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Biomedical subjects

R Langer

Publications and source records attributed to R Langer.

At least 325 records · Page 18Linked to original sources
PubMed1993

Prolonged regional nerve blockade by controlled release of local anesthetic from a biodegradable polymer matrix.

BACKGROUND: Prolonged nerve blockade is potentially useful in the management of many acute and chronic pain problems. Aside from infusions via an indwelling catheter, most currently available nondestructive techniques for prolonging local anesthetic action cannot provide more than 1-2 days of blockade. Bioerodible polymer matrixes have been used to deliver a variety of drugs in patients and animals for periods lasting weeks to years. Previously, dibucaine and bupivacaine were incorporated into copolymers of 1,3 bis(p-carboxyphenoxy) propane-sebacic acid anhydride (1:4), and demonstrated sustained release in vitro following incubation of the drug-polymer matrixes in phosphate-buffered solution (pH 7.4, 37 degrees C). METHODS: In the present study, cylindrical pellets made from polymer matrixes incorporated with bupivacaine-HCl were implanted surgically along the sciatic nerves of rats. Neural block was assessed by direct observation of motor skills and by leg-withdrawal latency to a hot surface. Biochemical and histologic examinations were performed 2 weeks after implantation. RESULTS: Sensory and motor blockade was produced for periods ranging from 2 to 6 days. Contralateral control legs receiving polymer implants without drug showed no block. Blockade was reversible, and animals appeared to recover sensory and motor function normally. Biochemical indexes of nerve and muscle function were indistinguishable from contralateral controls. CONCLUSIONS: This biodegradable polymer system provides a promising new alternative for the delivery of local anesthetics to peripheral nerves to produce prolonged blockade for the management of acute and chronic pain.

Anesthetics, Local↗
PubMed1993

Cell transplantation of genetically altered cells on biodegradable polymer scaffolds in syngeneic rats.

Many severe metabolic deficiencies in children are caused by a single gene defect with a resultant single gene product deficiency. These diseases may be amenable to permanent cure using new techniques of gene transfer and cell transplantation. In many in vivo models of retroviral mediated gene therapy, a significant limiting factor is the ability to transplant a sufficient number of modified cells. To potentially circumvent this problem, we have developed a biodegradable polymer implant system capable of supporting large numbers of genetically modified cells. In this study, we inserted a reporter gene into syngeneic cultured normal fibroblasts and then transplanted these genetically modified cells into animals using synthetic biodegradable polymer fibers as temporary cell delivery scaffolds. To begin to develop a system capable of delivering desirable proteins secreted by genetically modified cells, Fischer 344 adult rat fibroblasts were transduced in tissue culture with a retrovirus containing the reporter gene Lac Z. These genetically modified cells (1.1 x 10(7) cells/graft) were then attached to the biodegradable polymer fibers and the polymer-cell graft was transplanted subdermally into syngeneic recipients (n = 9). There was persistence of the modified cells with expression of the reporter gene for at least 30 days. The estimated number of genetically modified cells per implanted graft decreased from a pretransplant value of 1.1 +/- 0.6 x 10(7) to 3.2 +/- 0.7 x 10(6) by 15 days after transplantation (P < 0.01). Thereafter, the cell number did not vary significantly to the conclusion of the study at day 30 (3.6 +/- 1.0 x 10(6) cells/graft). Evidence of ingrowth and incorporation of other stromal elements was present in the graft by 1 week post-transplantation, as judged by counterstained hematoxylin and eosin micrograph sections. Migration of modified cells to areas outside of the polymer-cell graft was not detected. Over the course of the study, there was little degradation of the polymer implant, although by day 30, evidence of early dissolution was evident. The number of polymer fibers per high power field increased slightly from 62.5 +/- 5.8 on day 1 to 77.3 +/- 26.6 on day 30 (P > 0.2). These data suggest that the use of biodegradable polymer fibers may permit the transplantation of genetically modified cells in sufficient numbers to deliver a therapeutically useful product. Polymer matrices allow for the attachment and site-specific transplantation of genetically modified cells.

Animals↗
PubMed1993

Contrast-enhanced transcranial Doppler US with a new transpulmonary echo contrast agent based on saccharide microparticles.

The purpose of this first patient study (phase II) was to evaluate the clinical usefulness of a new echo contrast agent at transcranial Doppler ultrasonography (US). Twenty patients were selected from a group of 242 patients undergoing conventional transcranial Doppler US who had low (n = 18) or absent (n = 2) Doppler signals from the middle cerebral artery (MCA). The extent and duration of Doppler signal increase was measured in 30 MCAs and in 14 basilar arteries following the intravenous injection of a transpulmonary galactose microparticle suspension (SH U 508 A) at three concentrations (200, 300, and 400 mg/mL). Doppler waveform analysis became possible in 93% (28 of 30) of the MCAs following injection. The maximal increase in average Doppler signal intensity (11 dB at 200 mg/mL, 15 dB at 300 mg/mL, and 17 dB at 400 mg/mL) and the increase in average duration of the signal enhancement (163 seconds at 200 mg/mL, 219 seconds at 300 mg/mL, and 240 seconds at 400 mg/mL) depended on contrast agent concentration. Doppler waveform analysis became possible in 79% (11 of 14) of the basilar arteries. The intravenous injection of this new echo contrast agent markedly increases Doppler signal intensity in patients with nondiagnostic results at conventional Doppler US.

Basilar Artery↗
PubMed1993

Femoral head perfusion in patients with femoral neck fracture and femoral head necrosis.

Femoral head perfusion in adults was studied by superselective i.a. DSA in 35 normal subjects, in 9 patients with medial femoral neck fracture preoperatively, and in 36 patients with femoral head necrosis before bone grafting, and as therapeutic control after grafting. All patients with femoral neck fracture showed an interruption of the proximal nutrient branches. In 93% of the cases with femoral head necrosis, these branches were rarefied or the medial circumflex femoral artery was interrupted. Postoperative DSA after pedicled pelvic bone graft revealed a regularly perfused graft in 82%. Superselective i.a. DSA is a valuable procedure for the therapeutic decision in selected patients with femoral neck fracture as well as before pedicled pelvic bone grafting and as therapeutic control after grafting.

Adult↗
PubMed1993

Extracorporeal enzymatic removal of low density lipoproteins in rabbits: efficacy and safety.

An extracorporeal circuit incorporating a plasma separator reactor (PSR) was designed to modify low density lipoproteins (LDL). The PSR was tested in vivo with hypercholesterolemic New Zealand White rabbits. The bioreactor enzymatically converts LDL to a form that can be removed by the body at an enhanced rate. The physiological response of hypercholesterolemic New Zealand White rabbits to 90 minute extracorporeal treatments was monitored. The total plasma cholesterol concentration in the treated rabbits fell sharply (up to 40% decrease) during and following the treatment. Results of safety tests indicate no significant enzyme leaching from the device, no disruption or damage to erythrocytes, no increase in white blood cell count and no liver damage as indicated by five enzyme assays. All safety measurements suggest that the treatment is safe.

Animals↗
PubMed1993

[Primary femoral recanalization using a slowly rotating catheter system].

Over a period of 2 years, 26 patients with chronic occlusions of the superior femoral and popliteal arteries were referred for recanalization. In two cases, the origin of the superior femoral artery could not be detected. A primary recanalization was achieved in 21 of 24 patients by the catheter system used by us (Viadyn). A stent (extensor) had to be implanted in one case because of a considerable lesion of the intima. A short-term clot lysis was indicated for another patient. On the basis of our results, rotation angioplasty with a slowly rotating catheter system seems to be the therapeutic method of choice for chronic arterial occlusions in the thigh.

Aged↗
PubMed1993

[Imaging of the normal anatomy of the hand using high resolution magnetic resonance tomography and surface coils].

Magnetic resonance imaging can visualize the soft tissue and the bone marrow of the hand. High spatial resolution requires the use of a surface coil. Signal-to-noise contrast was measured and compared for 3 different coils. Optimal results were obtained with a surface coil with a diameter of 8.5 cm. The wrist and the fingers of 10 volunteers each were examined. Images with a high spatial resolution and a good signal/noise contrast were obtained, enabling the delineation of small structures like Gynon's channel and the median nerve.

Fingers↗
PubMed1993

[Bolus administration in spiral CT of the upper abdomen].

In 60 patients the density increases in the abdominal aorta and pancreas were examined quantitatively the visualisation of the arterial liver blood flow qualitatively in a test volume by means of spiral CT and a feed or speed differentiation of 10 mm/s for three different contrast medium boli. It was shown that during the entire study over 24 seconds the boli with 100 ml contrast medium at injection speeds of 3 ml/s and 50 ml contrast medium at 1.5 ml/s resulted in a continual density increase of the abdominal aorta from 221 to 265 Hounsfield Units (HU) or 161-167 HU, respectively. For measuring the abdominal aorta the bolus of 50 ml contrast medium at 3 ml/s was less suitable than the boli of 100 ml contrast medium with 3 ml/s and 50 ml with 3 ml/s because of the rapid in density from 250 to 118 HE. The bolus of 50 ml contrast medium and 3 ml/s, on the other hand, with 54 HU enhancement of the pancreas was approximately equal to the larger amount of contrast medium of 100 ml contrast medium and 3 ml/s with 56 HU, whereas 50 ml contrast medium and 1.5 ml/s with 46 HU was inferior. While all boli could sufficiently enhance the extrahepatic section of the hepatic artery, the larger amount of contrast of 100 ml proved to be superior to the other boli in the visualization of central intrahepatic vascular branches.

Adult↗
PubMed1992

Fetal malformations associated with chronic polyhydramnios in singleton pregnancies.

Forty-one congenital malformations were found in 28 newborns in a group of 197 cases of chronic polyhydramnios in singleton pregnancies. Of these, a total of 61% (17/28) was antenatally diagnosed ultrasonically. Nine newborns (4.5%) had malformations of the central nervous system (CNS), 9 (4.5%) cardiovascular malformations, 8 (4.1%) musculoskeletal anomalies, 7 (3.6%) malformations of the urinary and reproductive system, 4 (2%) respiratory system anomalies and 3 (1.6%) anomalies of the gastrointestinal system. Chromosomal abnormalities were found in three cases. As the association of polyhydramnios with fetal congenital anomalies is quite high (14.2% in our series), it is imperative to make a major effort to antenatally detect as many cases as possible. This means that in the case of hydramnios the following are required: ultrasound examination by an expert, echo ultrasonography when no other abnormalities are detected, and maybe even a chromosomal analysis.

Brain↗
PubMed1992

Antisense c-myb oligonucleotides inhibit intimal arterial smooth muscle cell accumulation in vivo.

Synthetic antisense oligonucleotides have been used to dissect gene function in vitro. Technical difficulties prevented the use of this approach for investigating the effect of gene products in vivo. Here we report the use of local delivery of antisense c-myb oligonucleotide to suppress intimal accumulation of rat carotid arterial smooth muscle cells. Our results suggest that antisense oligonucleotides can be used to define the in vivo biological role of specific macromolecules in the blood vessel wall and could potentially serve as a new class of therapeutic agents for cardiovascular disorders.

Animals↗
PubMed1992

Mechanical deformation of polymer matrix controlled release devices modulates drug release.

When magnetic fields were applied to polymer matrices of ethylene-vinyl acetate copolymer embedded with drug and a small magnet, drug release was increased up to 30-fold above baseline levels. It has been hypothesized that the effect of magnetic stimulation on the release of drugs from these matrices is the transduction of the applied magnetic field into a mechanical deformation of the matrix through motion of the magnet within the matrix. This current study provides support for this hypothesis by demonstrating that repeated pulsatile mechanical deformation of matrices can enhance the release of macromolecules from ethylene-vinyl acetate copolymer matrices. Furthermore, similar modulated release kinetics were obtained with mechanically compressed and magnetically stimulated matrices. We also established that modulation was dependent on the ratio of compression area to matrix volume and that modulation was maximized when this ratio was optimized.

Animals↗
PubMed1992

Switching from differentiation to growth in hepatocytes: control by extracellular matrix.

Studies were carried out to analyze how different extracellular matrix (ECM) molecules regulate hepatocyte growth and differentiation. Freshly isolated rat hepatocytes were cultured on non-adhesive plastic dishes that were pre-coated with defined densities of either laminin, fibronectin, type I collagen, or type IV collagen. Sparse cell plating densities were used to minimize cell-cell contact formation and all studies were carried out in chemically defined medium that contained a saturating amount of soluble growth factors. Dishes coated with a low ECM density (1 ng/cm2) supported hepatocyte attachment, but did not promote cell spreading or growth. Computerized image analysis confirmed that over 80% of cells remained free of contact with other cells under these conditions. Yet, these round cells maintained high levels of albumin gene expression as well as elevated secretion rates for multiple liver-specific proteins (albumin, transferrin, and fibrinogen), regardless of the type of ECM molecule used for cell attachment. When ECM coating densities were raised from 1 to 1,000 ng/cm2, cell spreading, expression of histone mRNA, DNA synthesis, and cell proliferation all increased in parallel. Activation of growth by high ECM densities was also accompanied by a concomitant down-regulation of differentiated functions and again, dishes coated with all four types of ECM molecules produced similar effects. Thus, the ability to switch hepatocytes from differentiation to growth (i.e., between different genetic programs) is not limited to a single ECM molecule, a distinct three dimensional ECM geometry, or due to alteration of cell-cell interactions. Rather, the regulatory signals conveyed by immobilized ECM molecules depend on the density at which they are presented and thus, on their ability to either prohibit or support cell spreading.

Animals↗
PubMed1992

Angiogenesis--biomedical technology.

All of these studies show that angiogenesis research can benefit from new biomedical technology tools currently being developed, as well as contribute by providing new technologies that can be used in other areas of medicine. It is hoped that the chapters in this book in this area will provide the reader with an up-to-date appreciation of some of the exciting research that is currently being pursued.

Animals↗
PubMed1992

Delivery systems for angiogenesis stimulators and inhibitors.

The development of biocompatible, controlled release systems for macromolecules has provided the opportunity to deliver angiogenesis stimulators and inhibitors. These systems have also facilitated the purification and characterization of a number of these substances. In this paper, we discuss controlled release delivery systems which release angiogenesis factors through either porous polymer matrices, degradable polymeric delivery systems or modulated polymer release systems.

Animals↗
PubMed1992

Angiopolarity of cell carriers: directional angiogenesis in resorbable liver cell transplantation devices.

The purpose of this study was to obtain directional angiogenesis of small blood vessels and capillaries to an implant made from a resorbable polymer for hepatocyte transplantation. It was intended to mimic the native acinar structure of the liver in order to facilitate replication of the cells and organ growth. The implant device structure was designed for injection to minimize surgical trauma. Hollow microspheres with an open porous wall structure and one large central opening were made from poly(d,l-lactic-co-glycolic acid) (85:15 lactic:glycolic). This polymeric scaffold was seeded with hepatocytes and implanted into the abdominal wall muscle of syngeneic Fisher rats. Specimens explanted up to 56 days p.o. showed hepatocyte survival and the development of a directional blood supply. This phenomenon is coined "angiopolarity". The study should help in addressing the issue as to whether avascular cell implants with post-transplantation organ growth should be attempted. Processing options in applying heat to the polymer solution allow manufacturing of larger microspheres with different diameters of central openings. This would allow the use of the scaffold for other cell transplantations than hepatocytes.

Animals↗