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Biomedical subjects

D Mooney

Publications and source records attributed to D Mooney.

At least 19 recordsLinked to original sources

A hydrogel material for plastic and reconstructive applications injected into the subcutaneous space of a sheep.

Soft tissue reconstruction using tissue-engineered constructs requires the development of materials that are biocompatible and support cell adhesion and growth. The objective of this study was to evaluate the use of macroporous hydrogel fragments that were formed using either unmodified alginate or alginate covalently linked with the fibronectin cell adhesion peptide RGD (alginate-RGD). These materials were injected into the subcutaneous space of adult, domesticated female sheep and harvested for histological comparisons at 1 and 3 months. In addition, the alginate-RGD porous fragments were seeded with autologous sheep preadipocytes isolated from the omentum, and these cell-based constructs were also implanted. The results from this study indicate that both the alginate and alginate-RGD subcutaneous implants supported tissue and vascular ingrowth. Furthermore, at all time points of the experiment, a minimal inflammatory response and capsule formation surrounding the implant were observed. The implanted materials also maintained their sizes over the 3-month study period. In addition, the alginate-RGD fragments supported the adhesion and proliferation of sheep preadipocytes, and adipose tissue was present within the transplant site of these cellular constructs, which was not present within the biomaterial control sites.

Absorbable Implants↗

In vivo characterization of a porous hydrogel material for use as a tissue bulking agent.

Tissue engineered biomaterial constructs are needed for plastic and reconstructive applications. To successfully form a space-filling tissue, the construct should induce a minimal inflammatory response, create minimal or no fibrotic capsule, and establish a vascular bed within the first few days after implantation to ensure survival of the implanted cells. In addition, the biomaterial should support cellular adhesion and induce tissue ingrowth. A macroporous hydrogel bead using sodium alginate covalently coupled with an arginine, glycine, and aspartic acid-containing peptide was created. A 6-month subcutaneous rat model study was performed to determine if the implanted material induced tissue ingrowth throughout the implantation area and maintained a three-dimensional vascular bed. The implanted materials produced a vascular bed, minimal inflammation and capsule formation, and good tissue ingrowth throughout the experiment. The material retained its bulking capacity by demonstration of no significant change of the cross-sectional area as measured from the center of the implants after the 2-week time point. In addition, the granulation tissue formed around the implant was loosely organized, and the surrounding tissue had integrated well with the implant. These results indicate that this material has the desired properties for the development of soft-tissue-engineering constructs.

Alginates↗

Growth and recombination of phage lambda in the presence of exonuclease V from Bacillus subtilis.

When expressed in Escherichia coli, the AddAB exonuclease/recombinase from Bacillus subtilis blocks the growth of phage lambda. Mutants of lambda that are deleted for ea47, a gene of unknown function which is expressed early in the lytic cycle, are not blocked for growth. The blocked-growth phenotype of lambda ea47+ in the presence of AddAB is expressed only when phage DNA replication is permitted.

Bacillus subtilis↗

Classification of the spectrum of Coats' disease as subtypes of idiopathic retinal telangiectasis with exudation.

PURPOSE: An increasing variety of eponymous terms have been used to describe atypical cases of Coats' disease. A group of typical cases of Coats' disease and other cases of differing severity were classified as one of four subtypes of idiopathic retinal telangiectasis with exudation and compared with regard to clinical outcome. METHODS: In a retrospective clinical review patients with typical and atypical Coats' disease were classified as severe, focal, juxtafoveal or associated (with another disease) forms of idiopathic retinal telangiectasis with exudation. RESULTS: 53 eyes in 50 patients were examined of which 62% (n=31) were male. 12 eyes were classified as severe (group 1), 22 focal (group 2), 12 juxtafoveal (group 3) and 7 associated (group 4). The mean age at diagnosis was lowest in group 1 eyes (6.8 years). The best visual acuity at presentation was 6/60 in group 1 whereas high proportions of eyes in the other groups had initial visual acuities of 6/24 or better. In group 1 only one eye was treated, the majority of eyes were blind or had been enucleated whereas 34 (79%) of eyes in the other groups were suitable for treatment and 29 eyes (67%) retained pre-treatment visual acuity or better at last follow-up. CONCLUSIONS: Idiopathic retinal telangiectasis with exudation is a spectrum of disease, which is synonymous with Coats' disease. In this retrospective study eyes with severe idiopathic retinal telangiectasis with exudation corresponding to typical Coats' disease, have poorer vision at presentation, are less suitable for treatment and have worse outcomes than eyes with other subtypes. The spectrum of disease severity seen in idiopathic retinal telangiectasis with exudation may be due to second somatic mutations in genes with an existing germline mutation (the two hit theory) and a mosaic phenotype.

Adolescent↗

Effectiveness of a planned strategy using cardiac rehabilitation nurses for the management of dyslipidemia in patients with coronary artery disease.

BACKGROUND: Firm evidence exists for reduction in mortality and morbidity by lipid-lowering therapy in patients with coronary artery disease (CAD), yet a significant proportion remain untreated. This prospective study determined the effectiveness of a planned strategy of management using a cardiac rehabilitation nurse in achieving (1) lower 6-month low-density lipoprotein (LDL) levels and (2) a higher proportion of patients on pharmacologic therapy. METHODS: A cardiac rehabilitation nurse arranged for the lipid profiles and initiated pharmacologic therapy as soon as possible after the diagnosis of CAD. In phase 1, this planned-strategy intervention group (n = 80) was compared with the usual-care control group (n = 189), where the management was left at the discretion of the attending cardiologist with the assignment to the 2 groups based on the weekly on-call rotations of the attending cardiologists in a nonrandomized manner. In phase 2 of the study all patients (n = 366) were enrolled in the planned strategy of management. RESULTS: There were no significant differences in the baseline lipid values between the control and intervention groups. The 6-month cholesterol and LDL values and the percentage of patients on lipid-lowering medications were significantly better in the intervention group (P =.01). In phase 2 the results obtained in the intervention group were duplicated in a much larger group of consecutive patients. The 6-month (millimoles per liter) results in the control, intervention, and phase 2 groups (respectively) were cholesterol 4.92 +/- 0.06, 4.60 +/- 0.07, 4.30 +/- 0.05; low-density lipoprotein 2.91 +/- 0.06, 2.68 +/- 0.07, 2.4 +/- 0.06; high-density lipoprotein 1.18 +/- 0.07, 1.12 +/- 0.09, 1.10 +/- 0.01; triglycerides 1.89 +/- 0.12, 1.78 +/- 0.09, 1.70 +/- 0.05; and on medications 49%, 83%, and 84%. CONCLUSION: A planned strategy of management with use of early pharmacologic therapy with a cardiac rehabilitation nurse assigned to obtain and follow lipid profiles and initiate therapy is more effective in controlling dyslipidemia than leaving the management to the cardiologist.

Alberta↗

Efficiency and cost saving of 7 day per week exercise testing utilizing all electrocardiography technologists.

BACKGROUND: In most centers, exercise testing (ET) is performed by one or two trained technologists during the weekdays (0800 hours-1600 hours), leaving a void during evenings and weekends. This leads to unnecessary increased costs due to delays in management of patients. Electrocardiography technologists (ECGT) are often available for extended hours. This project was undertaken to improve the efficiency of the ET laboratory by using ECGT to perform ET during these extended hours. METHODS: Clinical utility and cost saving of a 7 day per week ET for management of patients with suspected and/or known coronary artery disease utilizing ECGT was assessed after adequate training. Of 4099 patients undergoing ET between January 1995 and December 1997, 810 tests performed by ECGT were reviewed retrospectively. RESULTS: Of the 810 patients (age mean 58.4 +/- 0.44 yrs; range 16-88; males: 508, females: 302), 806 (99.5%) underwent the Bruce protocol. The indications were: diagnostic, 61.3%, predischarge acute myocardial infarction (AMI), 17.7%, evaluation of angina, 19.6%, other, 1.4%. Only 8 (0.1%) patients had complications (prolonged chest pain, 6; nonsustained ventricular tachycardia, 2) with no AMIs or deaths. This strategy resulted in a savings of 158 bed days (Can189,600 dollars) on inpatients and 15 bed days (Can18,000 dollars) on those presenting to the emergency department. CONCLUSIONS: This study demonstrates the feasibility and safety of utilizing ECGT for ET thus extending the hours of service. This resulted in efficient patient management, with a considerable cost-saving to the hospital.

Adolescent↗

Thermolabile MTHFR genotype and retinal vascular occlusive disease.

BACKGROUND: Raised levels of total plasma homocysteine (tHcy) are associated with an increased risk of retinal vascular occlusive disease. A thermolabile form of a pivotal enzyme in homocysteine metabolism, methylenetetrahydrofolate reductase (MTHFR), has been associated with vascular occlusive disease and raised tHcy levels. The relation between thermolabile MTHFR genotype, tHcy, and retinal vascular occlusive disease has not been determined. METHODS: A retrospective case-control study involving hospital based controls and cases with retinal vascular occlusions in whom tHcy levels had been determined was undertaken. Genotyping for the MTHFR 677 C-T mutation that specifies the thermolabile form of the enzyme was performed by established methods in all subjects. The relation between homozygosity for thermolabile MTHFR genotype (TT), raised tHcy levels, and risk of retinal vascular occlusive disease was examined. RESULTS: 87 cases of retinal vascular occlusive disease (mean age 68.7 years) comprising 26 cases of retinal artery occlusion and 61 of retinal vein occlusion were compared with 87 controls (mean age 70.2 years). The TT genotype did not confer a significantly increased risk of retinal vascular occlusive disease. The mean tHcy level was significantly higher in the cases than in the controls (p<0.0001). Overall, and in both the cases and controls, the frequency of the TT genotype was higher in those with normal tHcy levels than in those with increased levels of tHcy. However, the TT genotype did not significantly alter the risk of increased tHcy levels in these patients. CONCLUSIONS: The TT genotype is not associated with an increased risk of retinal vascular occlusive disease or increased tHcy levels in this group of elderly patients. In older patients, nutritional rather than genetic factors may be more important in increasing tHcy levels, a known risk factor for retinal vascular occlusive disease.

Aged↗

Tissue engineering's impact on dentistry.

Tissue engineering is a novel and exciting field that aims to re-create functional, healthy tissues and organs in order to replace diseased, dying, or dead tissues. The field has developed due to the inadequate supply of organs and tissues for patients requiring organ and tissue replacement. The following review first describes three major tissue engineering strategies. Although similar in their objectives, these strategies each maintain a unique component. Next, several examples of preclinical and clinical progress engineering oral-maxillofacial tissues are presented. Each of these examples highlights specific tissue engineering applications to different tissues of the oral-maxillofacial apparatus. Finally, practical implications are addressed as well as challenges that must be met in order for tissue engineering to reach its full potential.

Biocompatible Materials↗

Long-term follow-up of tissue-engineered intestine after anastomosis to native small bowel.

BACKGROUND: Our laboratory has investigated the fabrication of a tissue-engineered intestine using biodegradable polymer scaffolds. Previously we reported that isolated intestinal epithelial organoid units on biodegradable polymer scaffolds formed cysts and the neointestine was successfully anastomosed to the native small bowel. The purpose of this study was to observe the development of tissue-engineered intestine after anastomosis and to demonstrate the effect of the anastomosis over a 9-month period. METHODS: Microporous biodegradable polymer tubes were created from polyglycolic acid. Intestinal epithelial organoid units were harvested from neonatal Lewis rats and seeded onto the polymers, which were implanted into the abdominal cavity of adult male Lewis rats followed by 75% small bowel resection (n=24). Three weeks after implantation, the unit/polymer constructs were anastomosed to the native jejunum in a side-to-side fashion. The anastomosed tissue-engineered intestine was measured by laparotomy 10, 24, and 36 weeks after the implantation (n= 14). During the laparotomy, all rats with an obstruction in their anastomosis were killed and excluded from the statistical analysis. Another five rats were also killed at 10 and 36 weeks for histological and morphometric studies. RESULTS: All analyzed rats survived this study and significantly increased their body weight by 36 weeks. Obstruction of the anastomosis was observed in one rat at 24 weeks and in two rats at 36 weeks; however, the anastomosis was patent in the other 11 rats by 36 weeks. The tissue-engineered intestine of these 11 rats increased in length and diameter at 10, 24, and 36 weeks after anastomosis; there were statistically significant differences between each time point except between the length of 10 and 24 weeks (P<0.016 by Wilcoxon signed rank test). Histologically the inner surface of the tissue-engineered intestine was lined with well-developed neomucosa at 10 and 36 weeks; however, there were small bare areas lacking neomucosa in the tissue-engineered intestine at 36 weeks. Morphometric analysis demonstrated no significant differences in villus number, villus height, and surface length of the neomucosa at 10 and 36 weeks. CONCLUSIONS: Anastomosis between tissue-engineered intestine and native small bowel resulted in no complications after operation and maintained a high patency rate for up to 36 weeks. The tissue-engineered intestine increased in size and was lined with well-developed neomucosa for the duration of the study.

Anastomosis, Surgical↗

Detection and prevalence of early diabetic retinopathy in juvenile diabetics with diabetes for 10 years or more.

PURPOSE: To compare clinical examination using green light with clinical examination using white light in detecting early diabetic retinopathy (DR) in juvenile diabetic patients with disease for 10 or more years. METHODS: All patients were examined clinically using both green light and white light to determine the presence of DR. Each patient underwent seven-field fundus photography, which was used as the defined standard against which the clinical examinations were compared and also to determine the prevalence of DR. Data on age at diagnosis, duration of diabetes mellitus, recent HbA1c levels, treatment for systemic hypertension and microalbuminuria were obtained from medical records. RESULTS: When compared with the defined standard, fundal examination with green light was more sensitive, more specific and had higher predictive values than examination with white light in the detection of early DR. The overall prevalence of DR was 44%, which in all cases was classified as minimal to mild background DR. Patients with DR had significantly higher mean HbA1c levels than those without (p = 0.016). There was no significant association between the prevalence of DR and age at time of examination or diagnosis, duration of diabetes, patient gender, microalbuminuria levels or treatment for systemic hypertension. CONCLUSION: Fundal examination with green light is better than white light in detecting early DR in juvenile diabetics with duration of disease of 10 years or more. Furthermore the presence of DR is associated with poorer diabetic control. Due to coincident lifestyle changes and the probability of long duration of disease, accurate detection of early DR in juvenile diabetics with diabetes for over 10 years is important.

Adolescent↗

Acute stress disorder symptomatology during hospitalization for pediatric injury.

OBJECTIVE: To examine and identify predictors of acute stress disorder (ASD) and ASD symptomatology (ASDS) in children hospitalized for injuries. METHOD: Fifty-four youths were assessed while hospitalized for injuries. Dependent variables were parent and nurse ratings of children's ASDS. Independent variables included children's prior trauma exposure and behavior problems, injury severity and permanence, brain injury, injury or death to family/friend(s), parental distress, and child reports of the injury/hospitalization experience as meeting criterion A for ASD. RESULTS: A total of 92.6% of children felt the current experience met criterion A, compared with 64.8% of parents. According to parent questionnaires, 4 subjects (7.4%) met DSM-IV criteria for ASD while another 12 (22.2%) had clinically significant but subsyndromal ASDS. Children's ASDS, as reported by parents, correlated highly with parental distress and ratings of children's prior psychopathology, and modestly with injury severity and family/friend(s) injured or killed. Nurses' ratings of children's ASDS correlated strictly with injury- and accident-related variables, and not with parent ratings of children's ASDS. CONCLUSIONS: Children perceive injuries and hospitalizations as stressful. ASDS is widely though divergently reported by parents and nurses in children hospitalized for injury. Parental distress, children's prior psychopathology, and injury-related factors may be useful predictors of children's postinjury ASDS.

Acute Disease↗

Predicting posttraumatic stress after hospitalization for pediatric injury.

OBJECTIVE: To determine the prevalence and predictors of posttraumatic stress disorder (PTSD) in children after hospitalizations for accidental injuries. METHOD: Forty-eight children (aged 7-17 years) and their parents were assessed during hospitalization with measures of children's prior traumatization, prior psychopathology, injury severity, parental acute distress, and child acute distress. At outpatient follow-up at least 1 month later, children were evaluated for current PTSD diagnosis and PTSD symptomatology (PTSDS) by a child structured interview and for PTSDS by a parent questionnaire. RESULTS: A total of 12.5% had the full syndrome of PTSD at follow-up, and an additional 16.7% had partial (sub-syndromal) PTSD. Full PTSD was associated with a higher level of prior psychopathology, higher parental acute distress, and higher rates of prior sexual abuse, compared with partial or no PTSD. Prior psychopathology, parental distress, and, to a lesser extent, children's acute distress as reported by parents and breadth of prior traumatization, predicted subsequent PTSDS. CONCLUSIONS: Full or partial PTSD is relatively common in youths 1 month or more after hospitalization for injuries. Parents' acute distress as well as children's prior psychopathology, prior traumatization, and acute distress may be useful predictors of such injured children's subsequent PTSD or PTSDS.

Adolescent↗

Soft-tissue augmentation with injectable alginate and syngeneic fibroblasts.

Tissue engineering, a field that combines polymer scaffolds with isolated cell populations to create new tissue, may be applied to soft-tissue augmentation-an area in which polymers and cell populations have been injected independently. We have developed an inbred rat model in which the subcutaneous injection of a hydrogel, a form of polymer, under vacuum permits direct comparison of different materials in terms of both histologic behavior and their ability to maintain the specific shape and volume of a construct. Using this model, we compared three forms of calcium alginate, a synthetic hydrogel, over an 8-week period-standard alginate that was gelled following injection into animals (alginate post-gel), standard alginate that was gelled before injection into animals (alginate pre-gel) and alginate-RGD, to which the cell adhesion tripeptide RGD was linked covalently (RGD post-gel). Parallel groups that included cultured syngeneic fibroblasts suspended within each of these three gels were also evaluated (alginate post-gel plus cells, alginate pre-gel plus cells, and RGD post-gel plus cells). The study used 54 inbred Lewis rats (n = 9 for each of the six groups). Construct geometry was optimally maintained in the alginate post-gel group in which 58 percent of the original volume was preserved at 8 weeks and increased to 88 percent at 8 weeks when syngeneic fibroblasts were included within the gel. Volume was not as well preserved in the RGD post-gel group (25 percent of original volume at 8 weeks), but again increased when syngeneic fibroblasts were included (41 percent of original volume at 8 weeks). Maintenance of volume was poorest in the alginate pre-gel group (31 percent of original volume at 8 weeks) and failed to be augmented by the addition of fibroblasts (19 percent of original volume at 8 weeks). Histologically, the gel remained a uniform sheet surrounded by a fibrous capsule in the alginate post-gel groups. In the alginate pre-gel and RGD post-gel groups, there was significant ingrowth of a fibrovascular stroma into the gel with fragmentation of the construct. In constructs in which syngeneic fibroblasts were included, cells were visualized throughout the gel but did not extend processes or appear to contribute to new tissue formation. Material compression testing indicated that the alginate and RGD post-gel constructs became stiffer over a 12-week period, particularly in the cell-containing groups. Our results suggest that calcium alginate could be a suitable agent for soft-tissue augmentation when gelled subcutaneously following injection. The addition of syngeneic fibroblasts enhanced the ability of the gel to maintain the volume of a construct; this seems to be mediated by increased gel stiffness rather than by de novo tissue formation. Our animal model, in combination with material testing data, permits rigorous comparison of different materials used for soft-tissue augmentation.

Alginates↗

Raised plasma homocysteine as a risk factor for retinal vascular occlusive disease.

BACKGROUND/AIMS: A moderately elevated plasma concentration of the sulphur amino acid homocysteine is an independent risk factor for atherosclerotic vascular disease. Many of the risk factors associated with coronary, cerebral, and peripheral atherosclerotic vascular disease are common to retinal vascular occlusive disease but it is unclear whether elevated plasma concentrations of homocysteine are also associated with such disease. This study assessed the relation between retinal vascular occlusive disease and elevated levels of plasma total homocysteine (tHcy). METHODS: A retrospective case-control study involving hospital based controls and cases with retinal artery, central retinal vein (including hemiretinal vein), and branch retinal vein occlusions was performed. The relation between elevated tHcy, defined as a level greater than or equal to 12 micromol/l and risk of retinal vascular occlusive disease was examined. RESULTS: 87 cases of retinal vascular occlusive disease including 26 cases of retinal artery occlusion, 40 cases with central retinal vein occlusion, and 21 cases of branch retinal vein occlusion were compared with 87 age matched controls. Mean tHcy levels were higher in all disease groups and this difference was significant in patients with retinal artery occlusions (p= 0.032) and patients with central retinal vein occlusion (p=0.0001). When adjusted for known cardiovascular risk factors, tHcy was an independent risk factor for retinal vascular occlusive disease (OR 2.85 (95% CI 1.43-5.68)). CONCLUSIONS: Elevated tHcy is an independent risk factor for retinal vascular occlusive disease. Assessment of tHcy may be important in the investigation and management of patients with retinal vascular occlusive disease.

Aged↗

Managing chronic obstructive pulmonary disease in primary care.

Chronic obstructive pulmonary disease (COPD) causes significant morbidity in primary care. The main symptoms of COPD are cough and shortness of breath, while the main cause of the disease is smoking. It is a treatable condition, and to ensure best treatment it needs to be differentiated from asthma. Following the publication of guidelines by the British Thoracic Society in 1997, primary care has been given a framework for managing this condition. In primary care, COPD is best managed in a specific COPD clinic. This allows for staff training (both management decisions and techniques of lung infection monitoring), as well as presenting the patient with a therapeutic environment conducive to positive lifestyle education. This article discusses the setting up and running of a COPD clinic in primary care.

Adrenal Cortex Hormones↗