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Biomedical subjects

R Langer

Publications and source records attributed to R Langer.

At least 397 records · Page 22Linked to original sources
PubMed1990

New methods of drug delivery.

Conventional forms of drug administration generally rely on pills, eye drops, ointments, and intravenous solutions. Recently, a number of novel drug delivery approaches have been developed. These approaches include drug modification by chemical means, drug entrapment in small vesicles that are injected into the bloodstream, and drug entrapment within pumps or polymeric materials that are placed in desired bodily compartments (for example, the eye or beneath the skin). These techniques have already led to delivery systems that improve human health, and continued research may revolutionize the way many drugs are delivered.

Administration, Cutaneous↗
PubMed1990

Identification of an inhibitor of neovascularization from cartilage.

Certain tissues such as cartilage are resistant to vascular invasion, yet no single tissue-derived molecule that can inhibit angiogenesis has been reported. A protein derived from cartilage was purified that inhibits angiogenesis in vivo and capillary endothelial cell proliferation and migration in vitro in three separate bioassays. This protein is also an inhibitor of mammalian collagenase. These findings may help elucidate the mechanisms by which neovascularization is controlled in both normal and pathological states.

Adrenal Cortex↗
PubMed1990

Ectopic induction of cartilage and bone by water-soluble proteins from bovine bone using a polyanhydride delivery vehicle.

Controlled release delivery vehicles for water-soluble osteogenic proteins from demineralized bovine bone matrix were constructed using polyanhydride polymers. The water-soluble proteins were isolated from a 4 M guanidine hydrochloride extract of bone matrix. The water-soluble proteins possessed Chondrogenic Stimulating Activity (CSA) when tested in stage 24 chick limb bud cell cultures, but were incapable of inducing cartilage or bone in vivo when implanted intramuscularly into mice by themselves. The polyanhydride polymers alone were also incapable of inducing ectopic cartilage or bone. However, when the water-soluble proteins were incorporated into the polymeric delivery vehicle, the combination was capable of inducing cartilage and bone up to 50% of the time. These results demonstrate that it is possible to use polyanhydride polymers as controlled-release delivery vehicles for soluble bioactive factors that interact with a local cell population.

Animals↗
PubMed1990

Poly(anhydride) administration in high doses in vivo: studies of biocompatibility and toxicology.

Poly(anhydrides) proposed for use as vehicles for controlled drug delivery were administered subcutaneously in Sprague-Dawley rats at two dosage levels (800 mg/kg rat and 2400 mg/kg rat) for a period of eight weeks. Biocompatibility was assessed using a number of methods. Thirty-six clinical chemistry and hematology parameters were monitored throughout the study. Blood values were statistically analyzed for any possible effects due to the implanted polymer. After 8 weeks, rats were sacrificed and complete necropsies were performed. Histological evaluations of 33 organ sites including heart, lung, liver, kidney, and brain were performed. In addition, subcutaneous implant sites were excised and examined both grossly and microscopically. Results from evaluations of blood chemistry and hematology data, organ analyses and local implant site analyses overall demonstrated that the poly(anhydride) biomaterial possessed excellent in vivo biocompatibility.

Animals↗
PubMed1990

Ghosts of chromaffin granules accumulate biogenic amines according to a "pump and leak system" without contribution of carrier-mediated efflux.

Unidirectional inward transport into, accumulation by and loss of biogenic amines from ghosts of bovine chromaffin granules were studied to determine whether a carrier-mediated process contributes to the outward passage of amines across the granule membrane. In the presence of ATP-Mg2+, incubated ghosts (30 degrees C; pH 7.3) showed a reserpine-sensitive (IC50 2-5 nmol/l), unidirectional, inward transport of catecholamine (CA = 70% adrenaline/30% noradrenaline), 5-hydroxytryptamine (5-HT) and tyramine with different Km values (mumol/l: tyramine 2; 5-HT 5; CA 8) but with the same Vmax [20 nmol/(mg protein.min)] during the first 3 min of incubation. During longer incubation, the rate of unidirectional inward transport declined rapidly with time to about 30 to 40%, at which level it stayed nearly constant from 50 to 100 min of incubation. As the decline of unidirectional transport was independent of the amine accumulated in the ghosts, it is concluded that it reflects ageing of the membrane vesicles. During incubation for up to 100 min with CA, 5-HT or tyramine (10- to 30-fold Km) in the presence of ATP-Mg2+, the amine content of the ghosts increased, approaching a steady-state content (nmol amine/mg protein: CA 400-500, 5-HT 250, tyramine 60), which was negatively correlated with the lipid solubility of the amine (tyramine greater than 5-HT greater than CA), whereas the rate of approach to steady state (t1/2 in min: CA 20-30, 5-HT 7-10, tyramine less than 5) was positively correlated. Low concentrations of reserpine (greater than or equal to 25 nmol/l) caused net loss of amine from amine-loaded ghosts by inhibition of inward transport. However, reserpine did not reduce the fractional rate of loss (FRL) of CA-loaded ghosts induced by NH+4 or uncoupling agents. Accelerated exchange diffusion was not found to occur at the granule membrane, as addition of high concentrations of 5-HT or dopamine to CA-loaded ghosts did not result in a higher FRL of CA than did blockade of inward transport by reserpine. Analysis of steady-state kinetics revealed the following features of the granule transport. The approach to steady state (t1/2) was independent of the rate of inward transport. The steady-state amine content of ghosts approached a limiting value as the external concentration of the amine was increased; it was determined by the same kinetic constants (Km and the time-dependent Vmax) as found for the rate of carrier-mediated inward transport.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗
PubMed1990

The effect of large uterine fibroids on urinary bladder function and symptoms.

Fourteen patients with large uterine fibroids and urinary symptoms were treated with monthly injections of [D-Trp6]-luteinizing hormone-releasing hormone microcapsules. The average uterine size before treatment was 728 ml; it dropped to 323 ml (a drop of 55%) after treatment. Urinary symptoms of diurnal frequency disappeared in 11 of 12 patients (p less than 0.005) after the reduction of uterine size. Urgency decreased in 11 of 13 (p less than 0.005) and nocturia in eight of 10 (p less than 0.02). No differences were found before and after treatment in the symptoms of urge incontinence and stress incontinence in the cystometric and urethral pressure profile measurements. Urinary symptoms of frequency, urgency, and nocturia may be caused by the direct pressure exerted on the bladder by the enlarged uterus. Symptoms of urge incontinence and stress incontinence deserve a more specific treatment as they are not related to uterine size.

Adult↗
PubMed1990

Future directions in biomaterials.

Biomaterials have made a great impact on medicine. However, numerous challenges remain. This paper discusses three representative areas involving important medical problems. First, drug delivery systems; major considerations include drug-polymer interactions, drug transformation, diffusion properties of drugs and, if degradation occurs, of polymer degradation products through polymer matrices developing a more complete understanding of matrix degradation in the case of erodible polymers and developing new engineered polymers designed for specific purposes such as vaccination or pulsatile release. Second, cell-polymer interactions, including the fate of inert polymers, the use of polymers as templates for tissue regeneration and the study of polymers which aid cell transplantation. Third, orthopaedic biomaterials, including basic research in the behaviour of chondrocytes, osteocytes and connective tissue-free interfaces and applied research involving computer-aided design of biomaterials and the creation of orthopaedic biomaterials.

Biocompatible Materials↗
PubMed1990

Reproductive outcome after conservative surgery for unruptured tubal pregnancy--a 15-year experience.

The fertility outcome is presented in 118 patients after conservative surgery for unruptured tubal pregnancies. This patient group experienced 142 pregnancies, 127 of which were intrauterine (89.4%). The intrauterine pregnancies (IUPs) occurred in 83 patients (70.3%) and 63.5% (75/118) had live births. The recurrence rate of tubal pregnancy was 12.7%. Of the 65 patients with a normal contralateral tube 53 (81.5%) followed surgery with an IUP, 76.1% a live birth, and 7.7% a recurrent tubal pregnancy. Fifty-seven percent of the patients with a single tube followed with an IUP, and 47.6% had a live birth. The recurrence of tubal pregnancy in this group was 28.5%. Of the patients who underwent expression of tubal gestation, 60.6% followed with an IUP, and 57.5% with a live birth with no recurrence of tubal pregnancy.

Female↗
PubMed1990

Studies in rat liver perfusion for optimal harvest of hepatocytes.

Pediatric liver transplantation is successful but donor scarcity is a major limitation. We are studying hepatocyte transplantation as an alternative to provide functional hepatic replacement. This report details the study of rat liver perfusion for optimal harvest of hepatocytes and cell implantation. We performed 128 rat liver perfusions using a technique modified from the two-step enzymatic perfusion described by Seglen. We examined variations in the perfusion, rate, time, antegrade versus retrograde, pulsatile versus continuous flow, temperature, collagenase type, and variables of buffer composition. We have found optimal cell yield and viability under the following conditions: in situ perfusion, continuous flow at 25 cc/min, retrograde perfusion via the inferior vena cava, water bath temperature 38 degrees C, Boerhinger-Mannheim collagenase using a nonoxygenated HEPES based perfusion buffer, pH 7.4, for the initial perfusion and the same buffer with 4.8 mmol/L CaCl2 for the collagenase perfusion. These conditions consistently generate cell harvests of 500 to 700 x 10(5) cells/g of liver tissue with cell viability between 85% and 95%.

Animals↗
PubMed1990

Cervical internal os cerclage: description of a new technique and comparison with Shirodkar operation.

Internal os cerclage for cervical incompetence was performed in 90 patients who had previous McDonald procedure failure (70 patients) or had unfavorable cervical anatomy (short or lacerated cervix) for primary McDonald type cerclage (20 patients). Two different techniques were used: the Shirodkar operation (n = 44) with Mersilene band, and a simpler new technique (n = 46). The new technique is characterized by anterior colpotomy for exposure of the internal os, and a 0.6 mm nylon suture encircling the cervix to be tied high in the posterior fornix. The pregnancy outcome for both groups was similar. Late abortions of 8.7 and 11% and premature deliveries of 13 and 18% occurred in the new technique and the Shirodkar groups, respectively. The removal of the suture was generally difficult in the Shirodkar group and in eight patients analgesia and sedation were required. In the new technique group, the removal was easier and in only one patient was sedation required (p less than 0.0001). Severe vaginal discharge was found in 52% of the Shirodkar patients and none in the other group. Apparently the monofilament nylon suture prevented this side effect. It seems that the new technique is simpler to perform, involves fewer side effects, the removal of the suture is easier, and it is as effective as the Shirodkar procedure.

Cervix Uteri↗
PubMed1990

[Dynamic CT and angio-CT following liver transplantation].

This is a prospective study of the value of dynamic CT with a rapid scan frequency for the control of liver transplants. In 28 patients dynamic CT was performed with table movement and angio-CT without table movement, using a standard contrast bolus. In 97% of cases the central portions of the portal and hepatic veins could be delineated. The peripheral vessels were better demonstrated by angio-CT (79%) than by dynamic studies with table movement (47%). Parenchymal lesions, such as infarcts, and changes round the liver, such as lymphoedema or haematomas, were adequately demonstrated by either method. In addition, angio-CT provided information on abnormalities of perfusion within the transplant.

Adult↗
PubMed1990

[Differentiation of malignant liver tumors using rapid dynamic CT].

In this prospective study 39 patients with malignant liver tumours were examined by rapid CT. CT was performed before contrast, as dynamic CT, with and without table movement and, in some patients, images were obtained four hours after contrast injection. Time/density curves of hepato-cellular carcinomas (nine cases) showed more rapid and more intense enhancement of the tumour than of the liver parenchyma, whereas tumours of biliary origin (ten cases) showed a slower and less marked enhancement than surrounding tissue. In addition, it was possible to differentiate hypovascular metastases (18 cases) and hypervascular lesions by means of the time-density curve. Best diagnostic information was obtained by dynamic bolus CT. This method without table movement is best for differentiating focal lesions, whereas dynamic CT with table movement shows the extent and number of tumour lesions.

Adenoma, Bile Duct↗
PubMed1990

[Transcranial Doppler sonography. Normal values and physiologic changes].

In 100 normal subjects mean flow velocity in the middle (MCA), anterior (ACA), and posterior (PCA) cerebral arteries and mean pulsatility index were examined by transcranial Doppler ultrasound. Age-dependent normal reference values were assessed. The measured parameters showed a large variation increasing with age. The highest flow velocities were found in the MCA, the lowest in the PCA. The highest mean side difference in flow velocity was observed in the ACA. An increase of pulsatility index and a decrease of flow velocities in all examined vessels were found with increasing age. The influence of ventilation and heart function on flow velocity and pulsatility index was demonstrated by the investigation of 10 normal subjects in different phases of ventilation and 1 patient with aortic valve insufficiency.

Adult↗
PubMed1990

Enzymatically activated microencapsulated liposomes can provide pulsatile drug release.

A system for the delayed or pulsed release of biologically active substances was achieved by encapsulating liposomes containing the substance of interest inside microcapsules. The microcapsules retain the liposomes but allow controlled diffusion of the active substance when it is released from the liposomes. Furthermore, by coating the liposomes with phospholipase A2 (an enzyme that removes an acyl group from the 2 position of phospholipids) before placing them within the microcapsule, a pulsatile release pattern was achieved both in vitro and in vivo. The time of onset of the pulse as well as the release rate can be controlled by the amount of phospholipase A2, the molecular weight of the poly(L-lysine) that is used to coat the microencapsulated liposomes, and the composition of the phospholipid bilayer membrane. Even at 37 degrees C the system would protect a model enzyme (horseradish peroxidase). When not placed inside the microencapsulated liposomes, the enzyme lost its activity in solution at 37 degrees C in a few days, whereas it retained 40% of the initial activity after 30 days of incubation at 37 degrees C inside the microencapsulated liposomes.

Capsules↗
PubMed1990

Complete infraclavicular brachial plexus palsy with occlusion of axillary vessels following anterior dislocation of the shoulder joint.

Two cases of complete infraclavicular brachial plexus palsy after anterior dislocation of the shoulder joint are reported. Both patients had transient motor brachial plexus paralysis and extensive anesthesia of the whole upper limb. Additionally, one of them had occlusion of the axillary vessels. Vascular recovery occurred immediately after manipulation and reduction of the affected shoulder joint. Neurological recovery occurred 9 to 12 months later in both cases without surgery, other than closed reductions. Such neurological and vascular complications after anterior dislocation of the shoulder joint are unique.

Axillary Artery↗
PubMed1990

Hormonal changes related to impairment of cervical mucus in cycles stimulated by clomiphene citrate.

The levels of luteinizing hormone (LH), follicular stimulating hormone (FSH), 17-oestradiol (E2), progesterone (P), and testosterone (T) were determined for the early, midfollicular and periovulatory phase of spontaneous and clomiphene citrate (CC) induced cycles in 5 patients who responded with appearance of hostile cervical mucus (Group A) and 5 patients whose cervical mucus remained unchanged during the same treatment (Group B). The patients with hostile mucus were further investigated during a third cycle stimulated by CC and ethinyloestradiol (EE). Patients treated with CC for induction of ovulation who developed hostile cervical mucus showed higher levels of LH and T in the midfollicular phase of the menstrual cycle and significantly higher levels of T in the periovulatory period compared to patients with unchanged mucus. EE treatment induced a drop in the elevated LH and T levels and improved the cervical score. No change in E2 levels was noted. A direct effect of EE on the cervical glands together with the centrally mediated lowering of serum T are suggested to be responsible for improving the cervical mucus.

Cervix Mucus↗