PubMed Health⌕ Search

Biomedical subjects

R Langer

Publications and source records attributed to R Langer.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Transcranial Doppler ultrasound in internal carotid artery and middle cerebral artery disease.

Using noninvasive transcranial Doppler sonography, we studied cerebral collateral patterns in 30 patients with stenosis and/or occlusion of the extracranial internal carotid artery (ICA). All patients with unilateral ICA stenosis less than or equal to 80% had normal transcranial Doppler findings. 80% of patients with unilateral and 50% of patients with bilateral ICA stenosis of more than 80% including those with occlusion showed a collateralization via the ipsilateral anterior and/or posterior cerebral artery. 20% of patients with unilateral and 50% of patients with bilateral ICA stenoses of more than 80% (including occlusion) had two or three collateral pathways, including the ophthalmic artery. Another ten patients with stenosis or spasm of the middle cerebral artery (MCA) showed increased flow velocities with turbulence in the narrow segment. In four patients with severe MCA disease with a systolic peak velocity of more than 200 cm/s, the Doppler waveform distal to the lesion was damped. Decreased regional cerebral blood flow (rCBF) measured by 99mTc-HMPAO-SPECT was found in two patients with severe MCA stenosis. Another patient with moderate MCA stenosis with a systolic peak velocity of 140 cm/s showed a normal cerebral perfusion pattern.

Adolescent↗
PubMed1992

Biochemical and behavioral recovery in a rodent model of Parkinson's disease following stereotactic implantation of dopamine-containing liposomes.

We have developed and characterized dopamine-containing liposomes which exhibited in vitro sustained release of dopamine for over 40 days. These liposomes were stereotactically implanted into the partially denervated corpus striatum of rats subjected to unilateral lesions of the substantia nigra. In vivo release of dopamine into striatal extracellular fluid was monitored by microdialysis and behavior was assessed by quantifying apomorphine-induced asymmetric rotation. Extracellular dopamine levels in the partially denervated striatum of the dopamine liposome-treated rats were greater than the levels in the lesioned rats which received control liposomes and these levels remained elevated for 25 days. In parallel, those rats which received dopamine liposomes exhibited partial behavioral recovery, with attenuation of asymmetric rotation following systemic apomorphine administration. These results suggest that dopamine-containing liposomes can partially ameliorate the deficits associated with a rodent model of Parkinson's disease, and demonstrate the potential of this technology as a method for the controlled delivery of therapeutic agents into discrete areas of the brain.

Animals↗
PubMed1992

Methotrexate local injection for unruptured tubal pregnancy: an alternative to laparotomy?

Fifty-nine women with early unruptured tubal pregnancy were treated by a single local injection of methotrexate at laparoscopy. All 59 patients underwent the procedure without any adverse reaction, 47 (80%) of them needing no laparotomy. Twelve patients required a laparotomy for reasons such as rising beta-hCG levels and abdominal pain with or without rising levels of beta-hCG. Only one patient ruptured the tube. None of the women needed a blood transfusion. We found tubal patency in 19 out of 21 patients at follow up hysterosalpingography. Eleven pregnancies were subsequently reported, one of them tubal. The appearance of the injected tube was absolutely normal in three patients, one at cesarean section and two at repeated laparoscopy. No peritubal adhesions were observed. We suggest that this new technique is a safe and effective alternative to laparotomy in a patient with an early unruptured tubal pregnancy.

Adult↗
PubMed1992

Responsive polymer systems for controlled delivery of therapeutics.

The ideal drug-delivery system should provide therapeutics in response to physiological requirements, having the capacity to 'sense' changes and alter the drug-release process accordingly. Such responsive controlled delivery systems are still at an experimental stage. This review focuses on two basic approaches: (1) externally regulated systems (utilizing triggers such as magnetism, ultrasound, temperature and electricity), and (2) self-regulated systems (utilizing pH-sensitive polymers, enzyme-substrate reactions, competitive binding, and antibody interactions).

Animals↗
PubMed1992

Molecular weight changes in polymer erosion.

We report a study of the effects of polymer molecular weight on the erosion of polyanhydride copolymer matrices composed of 1,3-bis(p-carboxyphenoxy)-propane (CPP) and sebacic acid (SA) in aqueous solution. The erosion profile characteristically displays an induction period during which the erosion rate is relatively slow. The length of this period depends on the initial molecular weight of the polymer. The induction period may be characterized as a time during which a rapid decrease in polymer molecular weight occurs, the end of this period correlating with the time required for the polymer molecular weight to decrease to below a value of approximately 5000 (MW).

Decanoic Acids↗
PubMed1992

Controlled protein release from polyethyleneimine-coated poly(L-lactic acid)/pluronic blend matrices.

Protein release from degradable polymer matrices, composed of poly(L-lactic acid) and its blends with Pluronic surfactant, was investigated with and without the aqueous coating of an adsorptive water-soluble polymer, polyethyleneimine (PEI). PEI is a highly branched cationic polymer containing primary, secondary, and tertiary amino groups in its backbone. The treatment of PEI for PLA/Pluronic blend films exhibited a remarkable decrease in the "burst" release of protein at an initial stage and a significant extension in the protein release period. Protein release profiles could be controlled by varying PEI treatment time and its concentration. Our results suggest that PEI diffuses into the polymer matrices and crosslinks protein molecules by ionic interactions. Such a PEI-protein network near the surface region of matrix may act as a diffusional barrier for further release of protein molecules.

Delayed-Action Preparations↗
PubMed1992

[Cervical lymph node metastases. The sonographic demonstration of malignancy].

The value of sonography for demonstrating cervical lymph node metastases has been studied, using longitudinal and transverse measurements as criteria for malignancy. A transverse/longitudinal quotient greater than 2 indicates the presence of metastases with a 96% assurance. Using only longitudinal measurements lymph node metastases can be excluded with only a 36% assurance. The sensitivity of both methods also differs (95% for the maximal transverse quotient as against 90% for longitudinal measurements). The use of the maximal transverse quotient increases specificity from 36 to 96%. This gives sonography an accuracy of 95%.

False Negative Reactions↗
PubMed1992

Acetazolamide stimulation test in patients with unilateral internal carotid artery obstructions using transcranial Doppler and 99mTc-HM-PAO-Spect.

Fifteen patients with symptoms of cerebral ischaemia and angiographically confirmed unilateral stenoses or occlusions of the extracranial internal carotid artery (ICA) and 20 controls were studied by a 2 MHz transcranial Doppler (TCD) at rest and after stimulation with 1 g acetazolamide i.v., a cerebral vasodilator. In addition, the patients underwent 99mTc-HM-PAO-Spect measurement of regional cerebral blood flow (rCBF) at rest and after stimulation with 1 g acetazolamide. In 10 patients with ICA stenoses greater than 80% or occlusions, time-mean velocity (Vmean) increase and pulsatility index (PI) decrease in the postobstructive middle cerebral artery (MCA) as well as the increase of the ipsilateral rCBF were reduced in comparison with the contralateral side. The remaining 5 patients showed a normal Vmean increase and PI decrease in TCD.

Acetazolamide↗
PubMed1992

Isolation and characterization of an inhibitor of neovascularization from scapular chondrocytes.

An inhibitor of neovascularization from the conditioned media of scapular chondrocytes established and maintained in serum-free culture has been isolated and characterized. To determine whether this chondrocyte-derived inhibitor (ChDI) was capable of inhibiting neovascularization in vivo, this protein was assayed in the chick chorioallantoic membrane assay. ChDI was a potent inhibitor of angiogenesis in vivo (4 micrograms = 87% avascular zones). This inhibitor is also an inhibitor of fibroblast growth factor-stimulated capillary endothelial cell (EC) proliferation and migration, as well as being an inhibitor of mammalian collagenase. ChDI significantly suppressed capillary EC proliferation in a dose-dependent, reversible manner with an IC50 (the inhibitory concentration at which 50% inhibition is achieved) of 2.025 micrograms/ml. Inhibition by ChDI of growth factor-stimulated capillary EC migration was also observed using a modified Boyden chamber assay (IC50 = 255 ng/ml). SDS-PAGE analysis followed by silver staining of ChDI purified to apparent homogeneity revealed a single band having an M(r) of 35,550. Gel elution experiments demonstrated that only protein eluting at this molecular weight was anti-angiogenic. These studies are the first demonstration that chondrocytes in culture can produce a highly enriched, potent inhibitor of neovascularization which also inhibits collagenase.

Allantois↗