Biomedical subjects
Publications and source records attributed to R Langer.
Presented is a case of pneumococcal peritonitis in the presence of an IUD. The bacteriological identification was made by culturing material obtained via culdocentesis on admission. Treatment was conservative. The English literature is reviewed.
Many biological and biotechnological systems involve the diffusion of macromolecules through complicated macroporous (pore size on the order of 10-100 microns) environments. In this report, we present and evaluate an experimental system for measuring the rate of protein transport in an inert, macroporous membrane. For this particular membrane system, the microgeometry was characterized in terms of distribution of pore size, position, and orientation. Although the rate of protein desorption was much less than expected based on continuum diffusion models, we demonstrate that the measured transport rates are consistent with diffusion of protein in a complex, interconnected network of water-filled pores. The porous systems exhibit transitional behavior in quantitative agreement with the behavior of percolation lattices (mean square error 7%, n = 29). Predictive mathematical models of the diffusion process were developed: these models used percolation concepts to describe pore topology, continuum models of diffusion/dissolution to describe protein movement at each single pore, and measured pore size distributions. Effective diffusion coefficients for protein transport in aqueous, constricted macropores were predicted by this technique. Predicted diffusion coefficients, based on measured and derived microstructural parameters, agree with experimentally measured diffusion coefficients within a factor of 2. This approach may be useful in the design of porous polymer systems for biological applications and for evaluating other biological systems where conduction of mass, heat, momentum, or charge occurs in a heterogeneous environment.
Congenital anomalies of the müllerian system, the most common of which are uterine malformations, are associated with fertility problems. Multifactorial polygenic and familial factors are involved in their formation. The result may be deficient development (agenesis, rudimentary horn, unicornuate uterus), nonfusion (didelphys or bicornuate uterus), or defective canalization of the müllerian ducts (septate uterus). The principal diagnostic procedures include HSG, laparoscopy, hysteroscopy, and US. The clinical presentation varies from symptoms of obstruction of the menstrual flow in adolescence to hypomenorrhea and fertility problems in adult life. Repeated fetal loss, after excluding other reasons, is usually the indication for surgical intervention. Uterine septa should be resected hysteroscopically. A prophylactic cerclage has been suggested by various authors, including those of this work, in cases of symmetric uterine anomalies, especially bicornuate uteri, as a simple and effective treatment to be tried before embarking on major surgery such as metroplasty.
In a retrospective study, the clinical usefulness of digital image intensifier radiography was analysed. It could be demonstrated that for angiographic procedures the image quality of a 1024(2) matrix is superior to a 512(2) matrix. For digital excretory urography it could be seen that in 80 to 90% the images were at least sufficient to analyse the renal pelvis. Digital image intensifier radiography of bones was diagnostically sufficient in 76% and analysis of bone architecture was possible in 85%.
The effect of ultrasound on the degradation of polymers and the release rate of incorporated molecules within those polymers was examined. Up to 5-fold reversible increases in degradation rate and up to 20-fold reversible increases in release rate of incorporated molecules were observed with biodegradable polyanhydrides, polyglycolides, and polylactides. Up to 10-fold reversible increases in release rate of incorporated molecules within nonerodible ethylene/vinyl acetate copolymer were also observed. The release rate increased in proportion to the intensity of ultrasound. Temperature and mixing were relatively unimportant in effecting enhanced polymer degradation, whereas cavitation appeared to play a significant role. Increased release rates were also observed when ultrasound was applied to biodegradable polymers implanted in rats. Histological examination revealed no differences between normal rat skin and rat skin that had been exposed to ultrasonic radiation for 1 hr. With further study, ultrasound may prove useful as a way of externally regulating release rates from polymers in a variety of situations where on-demand release is required.
The biodegradable polyanhydrides are a new class of controlled release polymers developed for the interstitial delivery of drugs to their target site in the brain or other organs over periods ranging from days to years. These polymers can release molecules of any size in a predictable fashion. Their degradation products are non-cytotoxic and biocompatible. The biocompatibility of a biodegradable polyanhydride, the copolymer of poly[bis(p-carboxyphenoxy)propane] anhydride and sebacic acid (PCPP-SA) in a 50:50 formulation, was studied in the rabbit brain. Twenty adult New Zealand White male rabbits underwent implantation of PCPP-SA in a frontal lobe and absorbable gelatin sponge (Gelfoam) in the other frontal lobe. The animals were evaluated daily until the time of sacrifice. Groups of four animals were sacrificed sequentially on post-operative days 1, 3, 7, 21, and 60, and the brains processed for histological evaluation. None of the animals showed behavioral changes or neurological deficits suggestive of toxicity and all that received implants survived to their date of sacrifice. The histological examination showed no significant differences between the tissue reaction from PCPP-SA compared to Gelfoam. The polymers were also tested in the rabbit cornea bioassay and did not induce an inflammatory response. We conclude that PCPP-SA (50:50), a new biodegradable polymeric matrix that can be surgically implanted for the interstitial delivery of drugs in the brain, is biocompatible in the rabbit brain.
Sixty-five infertile women, 37 with anovulation, eight with ovulatory disturbances and 20 with unexplained infertility were treated by a combination of clomiphene citrate (CC) from cycle day 5 (or 3) and human menopausal gonadotrophin (HMG) begun 3 days later for induction or enhancement of ovulation. Monitoring was carried out by measuring preovulatory 17-beta-oestradiol (E2) and progesterone (P) concentrations in blood samples and by follicle measurements using ultrasound. Forty-seven pregnancies resulted with a multiple pregnancy rate of 7.7% for those completed. This incidence is very low and within the range found for CC induction and might result from the later commencement of stimulation compared with many other protocols. These results were achieved with a low incidence of ovarian hyperstimulation syndrome (2.6% per cycle). The HMG doses given were low in comparison with those found in other forms of induction. The deleterious effects of this combined mode of induction on cervical mucus and the occurrence of premature spontaneous ovulation were much less than in the sequential mode of treatment. These results suggest that combined induction treatment by CC and HMG as described offers a means of achieving low rates of multiple pregnancies a known complication in the induction of ovulation.
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In an earlier report of 86 elective Caesarean hysterectomies (1970-1979) we showed that the operation was associated with few complications but a high blood transfusion rate. In this paper we report an extended series comprised of 140 cases (1970-1986), and compare results of the 1970's series with that of the 1980's. The operative and postoperative complications were minimal during the entire period. The blood transfusion rate which was 64% in 86 cases of the 1970-1979 period decreased to 17% in 54 cases of the 1980-1986. Our results show that Caesarean hysterectomy is a safe procedure with some long-term advantages; therefore this option should be discussed with women who ask for tubal sterilization at the time of Caesarean section.
The effect of therapeutic range ultrasound (1 MHz) on skin permeation of D-mannitol, a highly polar sugar alcohol, inulin, a high molecular weight polysaccharide and physostigmine, a lipophilic anticholinesterase drug was studied in rats and guinea pigs. D-Mannitol and inulin are totally and rapidly excreted, once they have penetrated through the skin into the blood stream, permitting direct in vivo monitoring. For evaluating skin penetration of physostigmine the decrease of whole blood cholinesterase was measured. Ultrasound nearly completely eliminated the lag time usually associated with transdermal delivery of drugs. 3-5 min of ultrasound irradiation (1.5 W/cm2 continuous wave or 3 W/cm2 pulsed wave) increased the transdermal permeation of inulin and mannitol in rats by 5-20-fold within 1-2 h following ultrasound application. Ultrasound treatment also significantly increased (P less than 0.05) the inhibition of cholinesterase during the first hour after application in both physostigmine treated rats and guinea pigs: while in control guinea pigs no significant inhibition of cholinesterase could be detected during the first 2 h after application of physostigmine, the ultrasound treated group showed a 15 +/- 5% (mean +/- SEM) decrease in blood cholinesterase 1 h after ultrasound application. For physostigmine-treated rats the level of cholinesterase inhibition 1 h after ultrasound application was 53 +/- 5% in the ultrasound-treated group and 35 +/- 5% in the controls.
Jaundice, which is characterized by an excessive accumulation of bilirubin in the blood and tissues, occurs in 13% of newborns. The common treatments for neonatal jaundice are phototherapy and blood exchange transfusion. A novel approach using an extracorporeal blood filter containing immobilized bilirubin oxidase was recently proposed to detoxify jaundiced blood, and a prototype device markedly reduced serum bilirubin in genetically jaundiced Gunn rats. The primary toxicologic effect in that study was a 20% reduction in red blood cell count. Using a compartmental model for bilirubin metabolism, a mathematical simulation of the extracorporeal treatment's ability to reduce serum bilirubin levels in jaundiced infants is presented. Using a 10-mL reactor volume containing immobilized bilirubin oxidase, the simulation predicts a 32 to 65% decrease in plasma bilirubin concentration over a 4-h treatment for a 2 kg preterm hyperbilirubinemic newborn. In addition, a new approach to altering support material has essentially eliminated red blood cell lysis in vivo using Gunn rats and in vitro using adult blood.
In order to demonstrate the importance of ultrasound in the diagnosis of interstitial pregnancy, we present the following case, where sonographic findings were used as the sole proof of pregnancy and led to active surgical management.
In view of the role of the calcium ion in the inflammatory process, the effect of Diltiazem--a calcium antagonist--on the formation of intraperitoneal adhesions was studied in rats after induced trauma to the uterine serosa. It was found that intraperitoneal application of diltiazem inhibited adhesion formation to some extent, whereas intramuscularly administered Diltiazem did not. A dual effect of calcium antagonists on the formation of adhesions is suggested.
The following publication describes the diagnostic approach in different benign and malignant space-occupying lesions of the liver and pancreas. An essential prerequisite is that all imaging methods are actually available and can be made use of. While taking the cost factor into consideration, flow diagrams are worked out for haemangiomas, focal nodular hyperplasia, hepatocellular carcinoma and liver metastases, as well as for carcinoma of the pancreas and for insulinoma.
Since January 1983, 431 patients were examined by oral or rectal application of nonionic contrast medium for gastrointestinal studies. The contrast medium was uniformly well tolerated, even by severely ill preterm babies and infants. We present a review of our experience and a list of indications for the use of nonionic contrast media in gastrointestinal studies. In addition, the urinary iodine concentration of eight patients was examined after oral application of nonionic contrast medium in order to evaluate the resorption of the substance.
This prospective multicenter study analyzes the image quality and incidence of undesirable side effects in 2543 film and 1133 intravenous digital subtraction angiographic (DSA) examinations with iopromide. It can be shown that the frequency of undesired side effects in both methods is twice as high in patients at risk as in patients without special risk factors. The most frequent side effects are gastrointestinal and, in cerebral angiography, of a central nervous system nature. The image quality for 99% of the film angiographies was good or better. It could be demonstrated for the DSA that a higher iodine concentration of 370 mg I/ml tends to result in a reduction of the image quality with an increased rate of side effects.
In a prospective study, 150 threedimensional reconstructions of patients with bone diseases were analyzed. It could be seen that 3 D images were relevant for therapeutic considerations in diseases of craniofacial bones, and to a lesser degree for other skeletal regions. In no case was the 3 D reconstruction the only important factor for the therapeutic decision. The study demonstrated that 3 D imaging of the pelvic bones, especially for necroses of the femoral head, is severely limited without the possibility of computer-aided disarticulation.
A defined region of the right lobe of the liver was measured by grey scale analysis based on similar presets according to a manual input of a Region of Interest (ROI). During 20 days, the livers of healthy subjects were tested by this method in order to test the reproducibility of the results. By prospective studies, the livers of 30 patients were examined by ultrasound and CT regarding the determination of the extent of their fatty liver disease. The value of the density of liver was determined in Hounsfield units (HU). Both methods lead to parameters that characterise the fatty content of the liver. Statistic analysis shows acceptable correlation of both methods. By means of grey scale analysis in ultrasound measurements it is possible to estimate the extent of the fatty content of liver.