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Biomedical subjects

R Langer

Publications and source records attributed to R Langer.

At least 343 records · Page 19Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

[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↗

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↗

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↗

Oral treatment for jaundice using immobilized bilirubin oxidase.

Jaundice is characterized by an excessive accumulation of bilirubin in the blood and tissues. A novel approach to reduce plasma levels of bilirubin by blocking its enterohepatic circulation was investigated. The treatment consisted of oral administration of immobilized bilirubin oxidase, which could oxidize bilirubin in the intestine to less toxic and more water-soluble products. In vivo administration of 0.1 to 2.0 mg/day of immobilized enzyme over a four-day period to chronically jaundiced Gunn rats effectively lowered plasma bilirubin levels, but only when the molar ratio of total serum bilirubin to rat serum albumin (B/RSA) was larger than 0.35. Plasma bilirubin concentration decreased in that group from an initial value of 11.3 to 6.3 mg/dl (-40%, n = 5) after eight days. This decrease was statistically significant (p < 0.05 by Student's t test). However, administration of bilirubin oxidase to rats with a B/RSA ratio less than 0.35 (n = 10) resulted in no statistically significant change in plasma bilirubin concentration.

Administration, Oral↗

The development of polyanhydrides for drug delivery applications.

This paper reviews the development of the polyanhydrides as bioerodible polymers for drug delivery applications. The topics include design and synthesis of the polymer, physical properties, techniques to fabricate the polymer into drug delivery devices, evaluation of biocompatibility, and example applications of the polyanhydrides. Discussion of the interrelationship between the physical-chemical properties of the polyanhydrides, fabrication methods, and drug release rates is included. One section is devoted to a case study to provide a historical perspective of the development a polyanhydride-based drug delivery treatment from the conception of the idea to the final stages of human clinical trials. This section includes an outline of the extensive in vitro and in vivo testing that is necessary for development of a new material for biomedical applications.

Alzheimer Disease↗

[Cryopreservation of human erythrocytes with hydroxyethyl starch (HES)--Part 2: Analysis of survival].

Red blood cells (RBC) were obtained from 5 whole blood units by centrifugation and were purified using a simple washing procedure. Hematocrit and HES concentration in the 108-ml samples to be frozen were adjusted to 40% (v/v) and 12% (w/w), respectively. Cooling was performed by submerging into liquid nitrogen using containers to generate a flat sample geometry (3 mm thickness). After thawing in a shaking water bath, HES and free hemoglobin were removed in a simple washing step. To investigate the influence of the resuspension medium, the RBC were transferred into freshly drawn autologous plasma and into Locke's solution. Survival after thawing in terms of saline stability reached 86.3 +/- 2.3%. The cryopreservation procedure caused no major changes with regard to osmotic fragility, 2,3-DPG or intracellular Na+ and K+. ATP was reduced by 16%, but this had completely recovered after 3 h resuspension in autologous plasma. Some morphological changes present after thawing (e.g. stomatocytes, echinocytes) also recovered after 1.5 h. In conclusion, those RBC which survived the preservation process can be considered to be fully viable with regard to the parameters investigated.

Adult↗

[Cryopreservation of erythrocytes with hydroxyethyl starch. In vitro results leading to an autologous retransfusion model in the dog].

Although the effectiveness of hydroxyethyl starch (HES) as a cryoprotectant for human red blood cells (HRBC) is well known, no clinical application has evolved so far. In contrast to glycerol HES has the advantage of causing no hemolysis per se. This offers the opportunity of a one-step procedure without a time consuming postthaw washing procedure prior to transfusion. In this study the in vitro results obtained with red blood cells from 8 dogs (DRBC) are reported and compared to HRBC (n = 5). It turned out that DRBC had a similar 2,3-DPG and a lower ATP content. Postthaw survival in terms of saline stability differed markedly (67 +/- 6 and 86 +/- 2%, respectively). DRBC were more susceptible to hypotonic stress than HRBC. Nevertheless, after cryopreservation 91% (HRBC) and 92% (DRBC) of the original 2,3-DPG were found in the thawed RBC concentrates.

2,3-Diphosphoglycerate↗

[Rheologic studies before and after therapeutic cytapheresis and plasma exchange treatment].

Changes in rheological properties of human blood before and after platelet pheresis were measured in patients with myeloproliferative diseases as well as in a control group of platelet donors. Although the subjective feeling of the patients during measurement did improve, a better rheological situation could not be demonstrated by the rheological parameters used. A reduction of platelets does not influence the viscosity of whole blood or of plasma. On the other hand, the viscosities of whole blood and plasma differed significantly before and after plasma-pheresis in patients with monoclonal gammopathies. The control group comprised patients without hyperviscosity syndrome and did not show any change in rheological parameters.

Blood Component Removal↗

Effects of induced menopause on Burch colposuspension for urinary stress incontinence.

The clinical and urodynamic short term results after colposuspension for urinary stress incontinence has been studied in a group of young patients in whom menopause was induced surgically and compared with a similarly treated group who did not undergo surgical castration. Clinically, no differences were found in the incidence of diurnal frequency, nocturia, urgency, urge incontinence or stress incontinence between the groups. No urodynamic changes in the cystometric, uroflowmetry and urethral pressure profile measurements were found post-operatively between the two groups. It is concluded that surgically induced menopause in the absence of aging has no effect on the results of colposuspension for urinary stress incontinence in the short term.

Adult↗