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Biomedical subjects

R Langer

Publications and source records attributed to R Langer.

At least 199 records · Page 11Linked to original sources
PubMed1996

Initial clinical experience with spiral CT and 3D arterial reconstruction in intracranial aneurysms and arteriovenous malformations.

We studied 32 consecutive patients with known or suspected cerebrovascular abnormalities studied with spiral CT following a intravenous bolus injection of iodinated contrast medium with a power injector. Flow was 3 or 4 ml/s. In an attempt to define the appropriate delay time and scan duration a cranial angio-CT without table increment was performed on 10 patients. Enhancement was measured by manually placed regions of interest within the left middle cerebral artery and the inferior sagittal sinus. All patients except one had intraarterial angiography (DSA) for comparison. In 6 patients with an arteriovenous malformation (AVM) follow-up was possible after one and/or two embolisation procedures. These patients had plain and contrast-enhanced spiral CT. The diagnosis was aneurysm in 9 (8 berry aneurysms, one giant fusiform aneurysm), AVM in 13 (all supratentorial) and traumatic arteriovenous fistula in one. In 9 patients there were no detectable pathological vascular findings. After 3D reconstruction the size (between 5 and 28 mm), location and the relationship to the parent vessel of the aneurysms, the extent of the AVMs and the distribution of the embolisation material could be demonstrated clearly. The main feeding vessel(s), nidus and draining veins were reliably shown. The decreased extent of the AVMs after embolisation was clearly demonstrated. There was no difference in diagnosis when DSA and 3D-CT were compared by two independent radiologists. We consider arterial spiral CT with 3D reconstruction to have the potential of offering important diagnostic information for the treatment of intracranial AVMs and aneurysms.

Adult↗
PubMed1996

Abortion at 18-22 weeks by laminaria dilation and evacuation.

OBJECTIVE: To evaluate the complications of late second-trimester abortions (18-22 weeks) by laminaria dilation and evacuation, and the obstetric outcome of subsequent pregnancies. METHODS: Dilation of the cervix was achieved by repeated laminaria tent replacement. Evacuation was carried out in the outpatient clinic using general anesthesia. After the first menstrual period, all patients were invited for examination and thereafter were asked to report the outcome of subsequent pregnancies. RESULTS: One hundred seventy-one late second-trimester abortions were performed. Cervical dilation was satisfactory in 158 women (92%). Operative sonography was required in nine (5%) women. One had uterine atony. Follow-up from 150 (88%) women indicated no infection, but one woman required repeat curettage for retained products of conception. There was no indication of cervical injury on cervical internal os measurements remote from abortion. Of the 50 patients who conceived and elected to continue the subsequent pregnancies, two had premature deliveries unrelated to cervical incompetence, and all others reached term. CONCLUSION: Late second-trimester termination by laminaria dilation and evacuation is safe and probably not associated with future adverse pregnancy outcome.

Abortion, Induced↗
PubMed1996

In vitro degradation of a poly(propylene fumarate)-based composite material.

We investigated the in vitro degradation of a novel degradable polymeric composite material being developed to function as a temporary replacement for trabecular bone. This material is based on a mixture of poly(propylene fumarate) cross-linked by N-vinyl-pyrrolidone and includes sodium chloride and beta-tricalcium phosphate. Using an in vitro test in simulated body fluids, the compressive strengths and compressive moduli of two composite materials increased with degradation time and remained above the minimum values acceptable for trabecular bone substitutes. A compressive strength of 21.3 (+/- 0.4) MPa and a compressive modulus of 696 (+/- 53) MPa were measured after twelve weeks for a composite material with initial strength of 18.0 (+/- 4.6) MPa and initial modulus of 113 (+/- 40) MPa. This unexpected phenomenon may prove to be useful for orthopaedic applications.

Biocompatible Materials↗
PubMed1996

Stabilized polyglycolic acid fibre-based tubes for tissue engineering.

Polyglycolic acid (PGA) fibre meshes are attractive candidates to transplant cells, but they are incapable of resisting significant compressional forces. To stabilize PGA meshes, atomized solutions of poly(L-lactic acid) (PLLA) and a 50/50 copolymer of poly(D,L-lactic-co-glycolic acid) (PLGA) dissolved in chloroform were sprayed over meshes formed into hollow tubes. The PLLA and PLGA coated the PGA fibres and physically bonded adjacent fibres. The pattern and extent of bonding was controlled by the concentration of polymer in the atomized solution and the total mass of polymer sprayed on the device. The compression resistance of devices increased with the extent of bonding, and PLLA bonded tubes resisted larger compressive forces than PLGA bonded tubes. Tubes bonded with PLLA degraded more slowly than devices bonded with PLGA. Implantation of PLLA bonded tubes into rats revealed that the devices maintained their structure during fibrovascular tissue ingrowth, resulting in the formation of a tubular structure with a central lumen. The potential of these devices to engineer specific tissues was exhibited by the finding that smooth muscle cells and endothelial cells seeded onto devices in vitro formed a tubular tissue with appropriate cell distribution.

Animals↗
PubMed1996

Evolution of bone transplantation: molecular, cellular and tissue strategies to engineer human bone.

Bone defects occur in a wide variety of clinical situations, and their reconstruction to provide mechanical integrity to the skeleton is a necessary step in the patient's rehabilitation. The current gold standard for bone reconstruction, the autogenous bone graft, works well in many circumstances. However, autograft reconstruction, along with the available alternatives of allogenous bone graft or poly(methylmethacrylate) bone cement, do not solve all instances of bone deficiency. Novel materials, cellular transplantation and bioactive molecule delivery are being explored alone and in various combinations to address the problem of bone deficiency. The goal of these strategies is to exploit the body's natural ability to repair injured bone with new bone tissue, and to then remodel that new bone in response to the local stresses it experiences. In general, the strategies discussed in this paper attempt to provide the reconstructed region with appropriate initial mechanical properties, encourage new bone to form in the region, and then gradually degrade to allow the new bone to remodel and assume the mechanical support function. Several of the concepts presented below are already finding clinical applications in early patient trials.

Biocompatible Materials↗
PubMed1996

Novel approach to fabricate porous sponges of poly(D,L-lactic-co-glycolic acid) without the use of organic solvents.

A novel method was developed to produce highly porous sponges for potential use in tissue engineering, without the use of organic solvents. Highly porous sponges of biodegradable polymers are frequently utilized in tissue engineering both to transplant cells or growth factors, and to serve as a template for tissue regeneration. The processes utilized to fabricate sponges typically use organic solvents, but organic residues remaining in the sponges may be harmful to adherent cells, protein growth factors or nearby tissues. This report describes a technique to fabricate macroporous sponges from synthetic biodegradable polymers using high pressure carbon dioxide processing at room temperature. Solid discs of poly (D,L-lactic-co-glycolic acid) were saturated with CO2 by exposure to high pressure CO2 gas (5.5 MPa) for 72 h at room temperature. The solubility of the gas in the polymer was then rapidly decreased by reducing the CO2 gas pressure to atmospheric levels. This created a thermodynamic instability for the CO2 dissolved in the polymer discs, and resulted in the nucleation and growth of gas cells within the polymer matrix. Polymer sponges with large pores (approximately 100 microns) and porosities of up to 93% could be fabricated with this technique. The porosity of the sponges could be controlled by the perform production technique, and mixing crystalline and amorphous polymers. Fibre-reinforced foams could also be produced by placing polymer fibres within the polymer matrix before CO2 gas processing.

Biocompatible Materials↗
PubMed1996

Female urinary stress incontinence--does it have familial prevalence?

OBJECTIVE: Many factors have been suggested to contribute to the development of urinary stress incontinence in women. One of the suggested factors has been attributed to a genetic defect in the connective tissue in such patients. The purpose of this study was to evaluate the prevalence of urinary stress incontinence among relatives of patients with urinary stress incontinence. STUDY DESIGN: The prevalence of urinary stress incontinence among first-degree relatives was investigated in 259 females with urinary stress incontinence. A control group comprising 165 women without micturition disorders was randomly selected from our gynecologic outpatient clinic. The two groups were matched according to age, parity, maximal birth weight, and percentage of first-degree relatives on whom information was obtained. RESULTS: Data from 780 first-degree relatives in the study group and 474 in the control group were evaluated. We found that there was an overall prevalence of 20.3% (178/780) first-degree relatives in the study group compared with 7.8% (37/474) in the relatives of the control group (p<0.05). Among the mothers we found the prevalence of urinary stress incontinence to be 34.9% (71/203) in the study group compared with 12.7% (19/149) of mothers in the control group (p<0.005). Among the sisters in the study group the prevalence of urinary stress incontinence was 19.9% (73/367) compared with 6.8% (15/220) of sisters in the control group (p<0.005). Among the daughters we found the prevalence in the study group (6.7%) to be twice as high as in the control group (2.9%), but the difference did not reach statistical significance. CONCLUSIONS: The results of this study indicated a three-fold prevalence of urinary stress incontinence among first-degree relatives of female patients with urinary stress incontinence. This finding may support the theory of a genetic factor in the cause of urinary stress incontinence.

Adult↗
PubMed1996

Spontaneous vesicle formation at lipid bilayer membranes.

Unilamellar vesicles are observed to form spontaneously at planar lipid bilayers agitated by exothermic chemical reactions. The membrane-binding reaction between biotin and streptavidin, two strong transmembrane neutralization reactions, and a weak neutralization reaction involving an "antacid" buffer, all lead to spontaneous vesicle formation. This formation is most dramatic when a viscosity differential exists between the two phases bounding the membrane, in which case vesicles appear exclusively in the more viscous phase. A hydrodynamic analysis explains the phenomenon in terms of a membrane flow driven by liberated reaction energy, leading to vesicle formation. These results suggest that energy liberated by intra- and extracellular chemical reactions near or at cell and internal organelle membranes can play an important role in vesicle formation, membrane agitation, or enhanced transmembrane mass transfer.

Bacterial Proteins↗
PubMed1996

Imaging regions of transport across human stratum corneum during high-voltage and low-voltage exposures.

Scanning confocal fluorescence microscopy was used to image localized regions of calcein transport across human stratum corneum during constant low-voltage (iontophoresis) and pulsed high-voltage exposures. Following an electrical protocol, imaging revealed regions of fluorescence which were interpreted as sites where transport of a fluorescent probe (calcein) into the stratum corneum had taken place. Electrically-assisted transport of calcein, whether enhanced by iontophoresis or high-voltage pulsing, appears to occur through intercellular and, to some extent, transcellular pathways into localized regions of stratum corneum that are not associated with appendages. Uniquely associated with the highest voltage pulses used (300 V across the skin) was the appearance of small, brightly fluorescent areas containing nonfluorescent interiors, i.e., fluorescent "rings". We present evidence which suggests that the dark interiors represent sites through which transport occurred during pulsing, but where calcein was no longer present at the time of imaging. Transport of charged microspheres into the stratum corneum was also observed.

Biological Transport↗
PubMed1996

Characterization of glucose-mediated insulin release from implantable polymers.

We characterized a glucose-sensitive, controlled-release insulin delivery system. Insulin release rates increased when glucose was perfused in the release media surrounding the matrix. The system was composed of solid, particulate insulin, incorporated into an ethylene-vinyl acetate copolymer (EVAc) matrix. Feedback control was mediated by the glucose oxidase enzyme immobilized to Sepharose beads, which were incorporated along with insulin into the EVAc matrix. When glucose in solution entered the insulin delivery system, gluconic acid was produced, causing a drop in the microenvironmental pH of the matrix. This fall in pH resulted in a rise in insulin solubility and consequently a rise in the insulin release rate from the matrix. Insulin concentrations increased in vitro and in vivo in response to glucose infusion. The increased insulin release was shown to consist of a finite pulse of insulin that required an optimal recovery period of 1 h to achieve a maximal repeated response to a glucose stimulus. Repeated pulses were demonstrated over a 4 h period. An optimum enzyme ratio was also determined.

Animals↗
PubMed1996

Pulsed controlled-released system for potential use in vaccine delivery.

Biodegradable polymeric devices intended to provide a viable route for single-dose vaccination were developed using controlled-release technology. One of the main challenges in the development of these devices was to overcome several water-mediated inactivation processes that occur in conventional polymeric systems. Our strategy was focused on the prevention of antigen exposure to environmental conditions. For this purpose a microencapsulation process was designed and optimized to provide an inert and insulated environment for the bioactive material inside controlled-release systems. Tetanus toxoid (TT) was used as a model antigen. The systems consist of core-wall microcapsule structures in which the antigenic protein is entrapped into oil-based cores of TT surrounded by outer polymer shells made of poly(D,L-lactide-co-glycolide), thus potentially protecting the bioactive material against deleterious conditions. Furthermore, using these microcapsules, pulses of immunochemically detected TT were programmed to release at two different times (3 and 7 weeks), as corroborated by in vitro release studies. The engineering of these specific antigen release properties was possible by careful selection of the copolymer composition and molecular weight. The final formulations were characterized with respect to morphology, structure, size distribution, and amount of immunochemically detected TT encapsulated. The new systems offer the potential to control the manner and timing of delivery. Over 92% of the TT released over a 63 day period from these microcapsules was immunochemically detected.

Capsules↗
PubMed1996

Synergistic effects of chemical enhancers and therapeutic ultrasound on transdermal drug delivery.

The effects of (i) a series of chemical enhancers and (ii) the combination of these enhancers and therapeutic ultrasound (1 MHz, 1.4 W/cm2, continuous) on transdermal drug transport are investigated. A series of chemical enhancer formulations, including (i) polyethylene glycol 200 dilaurate (PEG), (ii) isopropyl myristate (IM), (iii) glycerol trioleate (GT), (iv) ethanol/pH 7.4 phosphate buffered saline in a 1:1 ratio (50% EtOH), (v) 50% EtOH saturated with linoleic acid (LA/EtOH), and (vi) phosphate buffered saline (PBS), as a control, are evaluated using corticosterone as a model drug. LA/EtOH is the most effective of these enhancers, increasing the corticosterone flux by 900-fold compared to that from PBS. Therapeutic ultrasound (1 MHz, 1.4 W/cm2, continuous) increases the corticosterone permeability from all of the enhancers examined by up to 14-fold (LA/EtOH) and increases the corticosterone flux from the saturated solutions by up to 13,000-fold (LA/EtOH), relative to that from PBS. Similar enhancements are obtained with LA/EtOH with and without ultrasound for four other model drugs, dexamethasone, estradiol, lidocaine, and testosterone. The permeability enhancements for all of these drugs resulting from the addition of linoleic acid to 50% EtOH increase with increasing drug molecular weight. Likewise, the permeability enhancement attained by ultrasound and LA/EtOH relative to passive EtOH exhibits a similar size dependence. A mechanistic explanation of this size dependence is provided. It is suggested that bilayer disordering agents, such as linoleic acid and ultrasound, transform the SC lipid bilayers into a fluid lipid bilayer phase or create a separate bulk oil phase. The difference in diffusivity of a given solute in SC bilayers and in either fluid bilayers or bulk oil is larger for larger solutes, thereby producing greater enhancements for larger solutes.

Administration, Cutaneous↗
PubMed1996

The secondary structure and aggregation of lyophilized tetanus toxoid.

Tetanus toxoid (TT), the vaccine for tetanus, is an important protein antigen and candidate for sustained release from polymeric matrices. During administration from the latter, the solid (e.g., lyophilized) protein will be exposed to elevated levels of temperature and moisture, conditions which trigger its aggregation. To examine the connection between this aggregation and the structure of the TT molecule in the solid state, Fourier-transform infrared (FTIR) spectroscopy was employed to determine the secondary structure of TT in the presence of various excipients. We found that excipient-free TT undergoes a significant alteration (mostly reversible) in the secondary structure during lyophilization. Specifically, more than half the total alpha-helix content was lost with a concomitant increase in beta-sheet structure. The extent of structural alterations in the presence of 1:5 (g:g protein) NaCl, sorbitol, or poly-(ethylene glycol), did not correlate with stability conferred towards moisture-induced aggregation. These results suggest that the degree of retention of the native protein structure in the dry state is not a general predictor of stability for the "wetted" solid within polymer controlled-release vehicles.

Excipients↗
PubMed1996

Quantification of insulin release from implantable polymer-based delivery systems and augmentation of therapeutic effect with simultaneous release of somatostatin.

Insulin injections control diabetes mellitus but do not reproduce physiologic regulation. Polymer-based controlled-release technology has enabled us to demonstrate: that the controlled release of insulin from polymer matrices can indeed be used to control diabetes mellitus but does so at the expense of hyperinsulinemia and hypoglycemia; and that somatostatin can be delivered in similar fashion, so as to provide glucose homeostasis in a more physiologic range, at lower insulin levels and at somatostatin doses below those used in intermittent infusion studies; and, that microgram quantities of a drug can be delivered successfully in vivo with intact biological function and in a manner that can be monitored continuously. In the present study the simultaneous polymer-matrix-controlled release of insulin with somatostatin extended glycemic control in diabetic rats. Eleven rats received subcutaneous polymer matrix implants containing insulin alone and 11 rats received implants containing insulin and somatostatin. Plasma and urinary glucose control were improved in both groups. Glucose concentrations in the insulin alone group remained depressed for 5 days until insulin release from the matrices declined below 11.6 units/kg/day. When somatostatin was delivered at 0.75-1.1 micrograms/kg/day together with insulin, plasma glucose control persisted for 12 days until insulin release decreased below 3.6 units/kg/day. It is our hope that further experiments regarding the potential role of both controlled-release devices and somatostatin will be performed to provide continuing therapeutic alternatives to the insulin-dependent diabetic. This is also the first in vivo demonstration of the simultaneous release of two biologically active peptide hormones from polymer matrices. The use of the polymer matrix systems may not only have profound effects on the ambulatory care of diabetes but might also permit the investigation of the synergistic effects of other families of compounds.

Animals↗
PubMed1996

Lectin-bearing polymerized liposomes as potential oral vaccine carriers.

PURPOSE: The potential of using lectin-modified polymerized liposomes as Peyer's patch targeted oral delivery vehicles was examined. METHODS: Two types of lectins, Ulex Europaeus Agglutinin I (UEA I) and Wheat Germ Agglutinin (WGA), were modified with a hydrophobic anchor N-glutaryl-phosphotidylethanolamine (NGPE). The modified lectins were incorporated into liposome bilayers and the liposomes were subsequently stabilized through polymerization. The presence of the lectins on the liposome surfaces was first confirmed with X-ray photoelectron spectroscopy. Surface-immobilized lectins were then shown to retain their carbohydrate binding activities as well as specificities based on an in vitro aggregation assay. Finally, delivery efficiencies of lectin-bearing liposomes were determined in mice. RESULTS: About 10.5% UEA I liposomes and 5.8% WGA liposomes were taken up from the gastrointestinal tract. These numbers are significantly higher than the 3.2% observed in the case of lectin-free liposomes. At the same time, UEA I liposomes exhibited the most effective Peyer's patch targeting among the three, which directly correlated with the highest delivery efficiency observed. CONCLUSIONS: This establishes that lectin modification of liposomes can promote binding to Peyer's patches, which will give improved efficiency for Peyer's patch targeted delivery. All these point to the potential for these lectin-modified liposomes as novel vehicles for oral vaccination.

Drug Carriers↗
PubMed1996

Transdermal drug delivery using low-frequency sonophoresis.

PURPOSE: Application of therapeutic ultrasound (frequency: 1-3 MHz and intensity: 0-2 W/cm2) enhances transdermal drug transport, although typically by a factor of less than 10. In this paper, we show that application of ultrasound at 20 KHz induces transdermal transport enhancements of up to 1000 times higher than those induced by therapeutic ultrasound. METHODS: In vitro (human cadaver epidermis) as well as in vivo (hairless rat skin) permeation experiments were performed to assess the effect of low-frequency ultrasound on transdermal transport. RESULTS: Application of low-frequency ultrasound (20 KHz, 125 mW/cm2, 100 msec pulses applied every second) enhanced transdermal transport of several permeants, including estradiol, salicylic acid, corticosterone, sucrose, aldosterone, water, and butanol, across human cadaver skin by a factor in the range of 3 to 3000 and that of salicylic acid across hairless rat skin in vivo by a factor of up to 300. Low-frequency ultrasound did not induce a long-term loss of the barrier properties of the skin (in vitro) or damage to living skin of hairless rats. At a mechanistic level, it is hypothesized that application of low-frequency ultrasound enhances transdermal transport through aqueous channels in the SC generated by cavitation-induced bilayer disordering. Support for this hypothesis is provided using experimental and theoretical analyses of low-frequency sonophoresis. CONCLUSIONS: Low-frequency ultrasound enhances transdermal transport of drugs more effectively than that induced by therapeutic ultrasound.

Administration, Cutaneous↗