A case of an umbilical mass as a primary presenting symptom of otherwise asymptomatic endometrial adenocarcinoma is reported. The pertinent literature is reviewed with regard to the relation of the umbilical mass to metastatic carcinoma.

Abdominal Neoplasms↗

PubMedDate not supplied

1994 Whitaker Lecture: polymers for drug delivery and tissue engineering.

This paper reviews three areas of the author's research. The first area concerns the development of technologies to release macromolecules continuously from solid polymers. By embedding solid protein (or other macromolecule) powders at the correct concentration in hydrophobic polymers, prolonged release for over 100 days can be achieved. The second area involves the synthesis of new biodegradable polymers specifically designed for drug delivery. A novel family of polymers, polyanhydrides, now being explored in a number of medical applications is examined. The use of these polymers to deliver chemotherapeutic agents locally may provide a new approach to treat brain cancer. The final research topic is in the area of tissue engineering. By placing mammalian cells on biodegradable polymer scaffolds, a variety of tissues have been created in animal models. Cartilage is discussed as a model tissue.

Animals↗

PubMedDate not supplied

Large scale preparation and characterization of mucopolysaccharase contamination free heparinase.

By a combination of hydroxylapatite chromatography and negative adsorption on QAE-Sephadex at pH 8.3, heparinase (E.C.4.2.2.7) can be successfully isolated from all the other mucopolysaccharase contaminants present in Flavobacterium heparinum. Hydroxylapatite isolates heparinase primarily from chondroitinases, hyaluronidase, and most glycuronidases. QAE-Sephadex chromatography at pH 8.3 further separates heparinase from heparitinases, sulfatases, and the remaining glycuronidases. The heparinase preparation thus obtained contains no statistically significant levels of other contaminating mucopolysaccharases except for heparitinases that are present at an apparent maximum level of 3.4%. Owing to the presence of a crossreaction of heparinase on heparitin sulfate at conditions employed for the assay of heparitinase, the heparitinase level of 3.4% could be misleading because of the action of heparinase on heparitin sulfate. Characterization of this heparinase preparation shows that the enzyme has an optimum salt concentration of 0.08M NaCl, an optimum pH of 6.5, an activation energy of 5 kcal/mol, and a Km of 7.95 X 10(-6) M. These parameters are almost identical to those displayed by a homogeneous heparinase preparation. The method described here is suitable for scale-up purposes using batch chromatographic procedures.

Chromatography, Gel↗

PubMedDate not supplied

An investigation of heparinase immobilization.

A systematic investigation of the parameters that affect the efficiency of immobilizing heparinase onto cyanogen bromide activated crosslinked 8% agarose beads was conducted. Two experimental measures, the "fraction bound" and the "fraction retained," were used to monitor the coupling efficiency. The fraction bound is the portion of the total initial enzyme that is bound to the agarose gel. The fraction retained is the fraction of bound enzyme that is active. The product of the two measures indicates the coupling efficiency. The activity of the immobilized heparinase was measured under conditions free of both internal and external mass transfer limitations, and thus, the fraction retained represents the true immobilized enzyme activity. Increasing the degree of activation of the beads results in an increase in the fraction bound, the fraction retained, and consequently, the coupling efficiency. As the ratio of enzyme solution to gel volume increases from 1.5 to 2.2, the fraction bound remains constant but the fraction retained decreases (heparinase concentration; 0.15 mg/mL and degree of activation; 9.5 mumol of cyanate esters/g of gel). At volume ratios greater than 2.2, both the fraction bound and the fraction retained decline continuously. Changing the heparinase concentration in the coupling solution changes the coupling efficiency in a manner similar to that of the volume ratio change. When heparin is added during the coupling process, the fraction bound declines as the heparin concentration increases, whereas the fraction retained increases up to a heparin concentration of 12 mg/mL and decreases thereafter. When arginine, lysine, and glycine are used to block the unreacted cyanate ester groups after the coupling process, the immobilized heparinase shows different pH optima of 6.5, 6.9, and 7.2, respectively. Based upon these findings, a protocol to optimize heparinase immobilization is developed.

Cross-Linking Reagents↗

PubMedDate not supplied

New directions in CNS drug delivery.

This commentary expands on the above article in 2 ways. First, it provides more recent information on polymer-based drug delivery systems. Second, it discusses experimental systems that may be clinically viable in the future such as prodrugs, cell-polymer transplants and gene transplants.

Brain Diseases↗

PubMedDate not supplied

Enhanced survival of transgenic hepatocytes expressing hepatocyte growth factor in hepatocyte tissue engineering.

Explore the source record for details and available documents.

Animals↗

PubMedDate not supplied

Degradation of porous poly(anhydride-co-imide) microspheres and implications for controlled macromolecule delivery.

The degradation properties of porous microspheres made using a new family of polyanhydride copolymers, the poly(anhydride-co-imides), were studied. Poly[trimellitylimido-L-tyrosine-co-sebacic acid-co-1,3-bis(carboxyphenoxy)propane] microspheres, with and without entrapped bovine serum albumin (BSA) as a model protein, were made using the double emulsion solvent evaporation process. Water penetration and anhydride bond cleavage (polymer degradation) occurred rapidly (< 5 days) compared to the time scale of overall microsphere erosion (weeks to months) with most polymer compositions. Subsequent to bond cleavage, the ultimate erosion of the microsphere and release of entrapped BSA was due mainly to the slow dissolution of the individual hydrophobic monomers (TMA-Tyr, SA and CPP) from the microsphere surface. BSA was released at approximately the same rate as the polymer eroded. Due to the fast degradation of anhydride bonds relative to microsphere erosion, initial polymer molecular weight did not have a significant effect on macromolecule release rates. Instead, monomer solubility correlated well with polymer erosion and BSA release rates. This erosion mechanism leads to predictable drug release rates which may be appropriate for the delivery of many protein therapeutics, including vaccine antigens. The anhydride-imide copolymers were well tolerated in acute toxicity studies in rats and therefore show promise as biomaterials.

Animals↗

PubMedDate not supplied

Computer simulation of low-density lipoprotein removal in the presence of a bioreactor containing phospholipase A2.

High concentrations of low-density lipoproteins (LDL) in the blood can lead to coronary heart disease, the primary cause of death in the Western hemisphere. A new treatment to reduce LDL levels is now being tested on rabbits, which are model animals for hypercholesteremia. The treatment involves using an immobilized enzyme within a bioreactor that is incorporated in an extracorporeal circuit. The enzyme modifies LDL to a form that is much more rapidly removed from the circulation. A mathematical model to describe LDL metabolism in the presence of the bioreactor was developed to give a better understanding of the biodistribution of modified LDL during and following treatment. A four-compartment model was developed on the basis of previous studies on human lipid metabolism, with the specific values of the constants taken from the experimental data on rabbits. A Macintosh II computer with a Stella II modeling program was used to simulate the treatment and to predict LDL levels over time given different values for initial enzyme activity, length of treatment, rate of enzyme denaturation, and other relevant parameters. The model provided a close fit with the experimental results for the change in total cholesterol. It confirmed the observed delay in the plasma cholesterol rebound level after the end of the extracorporeal treatment. One conclusion derived from both the experimental data and the model is that during the first 1.5 h, the limiting step for LDL removal is the rate at which modified LDL is taken up by the liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Dynamic cell seeding of polymer scaffolds for cartilage tissue engineering.

Cell seeding of three-dimensional polymer scaffolds is the first step of the cultivation of engineered tissues in bioreactors. Seeding requirements of large scaffolds to make implants for potential clinical use include: (a) high yield, to maximize the utilization of donor cells, (b) high kinetic rate, to minimize the time in suspension for anchorage-dependent and shear-sensitive cells, and (c) high and spatially uniform distribution of attached cells, for rapid and uniform tissue regeneration. Highly porous, fibrous polyglycolic acid scaffolds, 5-10 mm in diameter and 2-5 mm thick, were seeded with bovine articular chondrocytes in well-mixed spinner flasks. Essentially, all cells attached throughout the scaffold volume within 1 day. Mixing promoted the formation of 20-32-micron diameter cell aggregates that enhanced the kinetics of cell attachment without compromising the uniformity of cell distribution. The kinetics and possible mechanisms of cell seeding were related to the formation of cell aggregates by a simple mathematical model that can be used to optimize seeding conditions for cartilage tissue engineering.

Animals↗

PubMedDate not supplied

Primary peritoneal serous papillary carcinoma: a new epidemiologic trend? A matched-case comparison with ovarian serous papillary cancer.

The aim of the study was to examine the prevalence of primary peritoneal serous papillary carcinoma (PPSPC) as compared with ovarian serous papillary cancer (OSPC), and to study the clinicopathologic features and the frequency of germline BRCA1 and BRCA2 mutations in patients with PPSPC compared with those with OSPC. The study group included 28 cases of PPSPC. The comparison group included 35 female patients with OSPC, matched for stage, grade, and histologic subtype. All tumors were staged as either IIIB, IIIC or IV according to FIGO criteria. The patient characteristics, family and personal history of malignancies, the prevalence of germline BRCA mutations, clinicopathologic findings, presenting symptoms, pre- and intraoperative findings, and survival were compared in a matched-case retrospective study comparing patients with PPSPC vs. those with OSPC. Statistical analysis was made using Student's t-test, Chi-square, Wilcoxon, Kaplan-Meier and log-rank methods. Women with PPSPC had a significantly earlier menarche (P = 0.037) and a higher number or births (P = 0.03) than women with OSPC. No difference was found with regard to the prevalence of germline BRCA mutations in women with PPSPC compared with women with OSPC (7.1% vs. 25.7%). There was a significant increase (P = 0.02) in the incidence of abdominal distension as reported by PPSPC (64%) vs. OSPC patients (26%). Significantly more women with PPSPC than with OSPC presented with clinical ascites (P = 0.0001) and without palpable pelvic mass (P = 0.000001). On exploratory laparotomy, significantly more women with PPSPC than with OSPC had a minimal disease in the pelvis (P = 0.0087). Three-year survival analysis demonstrated a significantly worse survival rate for the PPSPC group than for the OSPC group (P = 0.017). A significant increase in the prevalence of PPSPC compared with OSPC was observed during the study years (P = 0.00001). We concluded that PPSPC and OSPC might be two distinct cancers, presenting a new epidemiologic trend regarding the increased incidence of PPSPC.

Case-Control Studies↗

PubMedDate not supplied

[Ewing's sarcoma of the rib].

In addition to eosinophilic granuloma, chondroma, osteochondroma, aneurysmatic bone cyst, and osteomyelitis, the differential diagnosis of primary costal tumors in children must also include Ewing's sarcoma. Radiologic diagnostic problems in localizing the tumor, in differential diagnosis, and the importance of imaging procedures are discussed with reference to a 16-year-old female patient.

Adolescent↗

PubMedDate not supplied

[Sonography of the hip in underweight premature infants].

In a prospective study 120 hips of preterm babies below 2,000 g were investigated by ultrasound studies in order to determine the distribution of the types according to Graf's classification. Compared with unselected newborns, preterm babies show a significantly higher incidence of ultrasound types Ib and IIa. The distribution of the ultrasound types of the hips of both groups is compared.

Female↗

PubMedDate not supplied

[Intrapericardial diaphragmatic hernia].

Report of a case with congenital right sided intrapericardial diaphragmatic hernia. This type of a congenital diaphragmatic hernia occurs only rarely. Until 1984 30 cases are recorded in the available literature.

Diagnosis, Differential↗