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Biomedical subjects

D Mooney

Publications and source records attributed to D Mooney.

At least 55 records · Page 3Linked to original sources

Tissue-engineered growth of cartilage: the effect of varying the concentration of chondrocytes seeded onto synthetic polymer matrices.

Ninety-six synthetic bioresorbable cell-delivery devices (10 x 10 x 0.5 mm) were seeded, varying the concentrations of living chondrocytes (2, 10, 20, 100 million cells/cc) isolated from shoulders of freshly killed calves and implanted subcutaneously on the dorsum of nude mice after 1 week of in vitro culture. This resulted in the formation of new cartilage in 95.6% of the implants. Twenty-four control implants (0 cells seeded) did not show cartilage formation. During 12 weeks of in vivo implantation, the wet weight and the thickness of the specimens (10, 20, 100 million cells/cc) increased significantly. Histologic analysis revealed cells appearing in their own lacunar structures surrounded by basophilic matrix. The increase in sulfated glycosaminoglycan content indicated the maturation of the extracellular matrix. The ability to manipulate the growth of new cartilage on biocompatible polymer scaffolds by varying the cell density before in vivo implantation will allow engineering to optimize the utilization of chondrocytes in relation to the desired shape, thickness, and quality of the new cartilage.

Animals↗

Alzheimer's disease: a new hope.

Until recently, the diagnosis and treatment of Alzheimer's disease was limited. This article describes the outcome of new research and advances in the pharmacological treatment of this disease, especially the use of Cognex (tacrine). It also reports on a multicenter study of tacrine we participated in with patients at Raleigh Psychiatric Services, Inc. in Beckley.

Aged↗

Cartilage engineered in predetermined shapes employing cell transplantation on synthetic biodegradable polymers.

Cartilage is often used as structural support tissue for cosmetic repair in plastic and reconstructive surgery. We describe the efficacy of a new approach for the generation of cartilage in predetermined shapes using specially configured biodegradable synthetic polymer devices as delivery vehicles for transplanted cells. Synthetic biodegradable polymer scaffolds were configured in one of four specific shapes, i.e., a triangle, a rectangle, a cross, and a cylinder. The polymer matrices were seeded with freshly isolated bovine articular chondrocytes and then implanted subcutaneously into nude mice. Gross examination of excised specimens 12 weeks after implantation revealed the presence of new hyaline cartilage of approximately the same dimensions as the original construct. This cartilage showed no signs of resorption or overgrowth over the 12-week time course of the experiment. Histologic evaluation using hematoxylin and eosin stains confirmed the presence of normal mature hyaline cartilage in 46 of 48 specimens. These results suggest that cartilage can be created in predetermined shapes and dimensions using cell transplantation on appropriate polymer templates. This technology would be useful in cosmetic and reconstructive surgery.

Animals↗

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↗

Disk drusen and angioid streaks in pseudoxanthoma elasticum.

Visual field loss secondary to optic disk drusen became evident before the development of angioid streaks in a patient with pseudoxanthoma elasticum. The incidence of optic disk drusen in cases of pseudoxanthoma elasticum is 20 to 50 times greater than that in the healthy population. We postulate that the abnormal aggregation of macromolecules with a high affinity for calcium (resulting in abnormalities in elastin in cases of pseudoxanthoma elasticum) also develops at the cribriform plate, disrupting axonal flow and leading to disk drusen formation. Pseudoxanthoma elasticum is associated with marked cardiovascular and gastrointestinal morbidity. Moreover, macular hemorrhage and precipitation of angioid streaks have frequently been noted after trauma. Prompt diagnosis of pseudoxanthoma elasticum will allow necessary prophylaxis and must be considered in patients with optic disk drusen.

Adult↗

Serologic response to treatment of infectious syphilis.

OBJECTIVE: To evaluate the serologic response to treatment of patients with infectious syphilis. DESIGN: Historical cohort study of all cases of infectious syphilis in Alberta from 1981 to 1987. PATIENTS: A total of 1090 patients were entered; 857 with primary syphilis, 183 with secondary syphilis, and 50 with early latent disease. Two hundred and eight patients were excluded who either were pregnant, had negative serologic results before treatment, had clinical relapse, were treatment failures, or were lost to follow-up. INTERVENTIONS: All 882 evaluable patients were treated with a recommended antibiotic regimen for infectious syphilis and returned for re-assessment including repeat serologic testing. MEASUREMENTS AND MAIN RESULTS: Seventy-two percent (95% CI, 66% to 77%) and 56% (CI, 43% to 70%) of patients with initial episodes of primary or secondary syphilis had seroreverted according to rapid plasma reagin (RPR) test results by 36 months. A 2- and 3-tube decline was seen by 6 and 12 months in primary and secondary syphilis. Early latent syphilis resulted in only a 2-tube decrease at 12 months. Serologic response was not affected by sex, age, race, or sexual orientation. Patients with their first infection were more likely to experience RPR seroreversal than those with repeat infections. The RPR reversal rates also depended on the pretreatment titer and stage of disease. At 36 months, 24% (CI, 20% to 28%) of patients had nonreactive fluorescent treponemal antibody absorption tests (FTA-Abs), and 13% (CI, 11% to 15%) had nonreactive microhemoglutination tests for Treponema pallidum (MHA-TP). CONCLUSIONS: Adequate therapeutic response for syphilis must be based on illness episode and the pretreatment RPR titer. Treponemal tests can demonstrate seroreversion after 36 months, and a negative treponemal test does not rule out a past history of syphilis.

Alberta↗

Tissue engineering by cell transplantation using degradable polymer substrates.

This paper reviews our research in developing novel matrices for cell transplantation using bioresorbable polymers. We focus on applications to liver and cartilage as paradigms for regeneration of metabolic and structural tissue, but review the approach in the context of cell transplantation as a whole. Important engineering issues in the design of successful devices are the surface chemistry and surface microstructure, which influence the ability of the cells to attach, grow, and function normally; the porosity and macroscopic dimensions, which affect the transport of nutrients to the implanted cells; the shape, which may be necessary for proper function in tissues like cartilage; and the choice of implantation site, which may be dictated by the total mass of the implant and which may influence the dimensions of the device by the available vascularity. Studies show that both liver and cartilage cells can be transplanted in small animals using this approach.

Animals↗

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↗

Intraocular lens power calculation.

Accurate intraocular lens power calculation is an important adjunct to the technique of extracapsular cataract extraction. An increasing number of ophthalmologists now perform preoperative biometry routinely. We studied a group of fifty patients and analysed the accuracy of intraocular lens power calculation using the SRK formula.

Adult↗

Regional choroidal atrophy and alopecia. A new syndrome.

Two siblings with total regional choroidal atrophy and other manifestations of ectodermal dysplasia are presented. The mode of inheritance is uncertain, but mild macular disease in the father may represent heterozygote manifestation of a recessive condition.

Adult↗

Newborn duodenal atresia: an improving outlook.

From 1973 through 1983, 20 newborns with congenital duodenal atresia were treated. These patients are compared with our previous series and with other published series. There were no fatalities among the 19 patients who underwent operation, an improvement from the 72 percent survival rate in our previous series. Fifty-five percent of the patients had associated congenital anomalies, which frequently complicated their management. The use of a transanastomotic jejunal feeding tube resulted in delayed oral feeding and prolonged hospitalization, and cannot be recommended.

Abnormalities, Multiple↗

Duodenal atresia: a comparison of techniques of repair.

Although duodenal atresia is a common cause of congenital intestinal obstruction, the optimal technique of repair remains controversial. In a 10-year period, 41 newborns (20 male, 25 premature) underwent either side-to-side duodenoduodenostomy (SDD, 10 infants), side-to-side duodenojejunostomy (SDJ, 9 infants), or diamond-shaped duodenoduodenostomy (DDD, 22 infants) in a nonrandomized series. One-layer anastomosis was used in each case, and gastrostomy was placed in most patients. Groups were compared for survival, prematurity, associated anomalies, time until feeding onset, total hospitalization time, and complications. The three groups were identical for survival (all 100%), prematurity (60% SDD, 67% SDJ, 59% DDD), and serious associated anomalies (cardiac, gastrointestinal, Down's; 33% SDD, 44% SDJ, 50% DDD). The time until feeding onset was shortest with DDD (4.1 +/- 0.4 days), compared with 8.0 +/- 1.1 days for SDD and 9.6 +/- 1.9 days for SDJ (both P less than .05 v DDD). Total hospitalization was significantly less in DDD (16.2 +/- 2.1 days) v 24.2 +/- 3.1 days for SDD (P less than .05) and 28.3 +/- 4.3 days for SDJ (P less than .01). One complication necessitating reoperation occurred in each group (SDD, adhesions; SDJ, stenotic anastomosis; and DDD, missed second atresia). These data suggest that DDD is superior to SDD and SDJ for repair of duodenal atresia, resulting in earlier feeding and discharge.

Duodenal Obstruction↗

The in-vitro activity of some antimicrobial agents against methicillin-resistant Staphylococcus aureus.

A total of 185 strains of methicillin resistant Staphylococcus aureus was investigated for sensitivity to five other antimicrobial agents. The vast majority of these strains were also resistant to gentamicin and fusidic acid. Rifampicin was the most active drug tested (MIC90, 0.007 mg/l), while two newer compounds teichomycin and ciprofloxacin showed equal and appreciable activity (MIC90, 0.5 mg/l).

Anti-Bacterial Agents↗