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Biomedical subjects

G A Thomas

Publications and source records attributed to G A Thomas.

At least 91 records · Page 5Linked to original sources

Interactive computer teaching/learning in the dental curriculum: partial denture design.

Interactive multimedia is an emerging industry with a broad domain. It operates from a base of computer technology to enable the production, distribution and sharing of ideas. The use of multimedia in the educational setting is in keeping with the concept of learning, rather than teaching and, with this in mind, a pilot program in interactive computer learning has been developed which is geared specifically to the requirements of junior students. The design sequence and philosophy used in this program follow the teaching at Sydney University Dental School. Its purpose is to facilitate students in mastering the technical aspects of denture framework design, leading them through a set sequence of steps from saddle identification to finish. Future plans, using more sophisticated equipment, are to develop more advanced programs for senior (fourth year) students, including applications for treatment planning and also the rudiments of osseointegrated implant work.

Australia↗

Transdermal nicotine for active ulcerative colitis.

BACKGROUND: Ulcerative colitis is largely a disease of nonsmokers. Because anecdotal reports suggest that smoking and nicotine may improve the symptoms of the disease, we examined the effect of nicotine as a supplemental treatment for ulcerative colitis. METHODS: We treated 72 patients with active ulcerative colitis with either transdermal nicotine patches or placebo patches for six weeks in a randomized, double-blind study. Incremental doses of nicotine were given; most patients tolerated doses of 15 to 25 mg per 24 hours. All the patients had been taking mesalamine, and 12 were receiving low doses of glucocorticoids; these medications were continued without change during the study. Clinical, sigmoidoscopic, and histologic assessments were made at base line and at the end of the study; symptoms were recorded daily on a diary card, and the clinician made a global assessment. Side effects and plasma nicotine and cotinine concentrations were monitored throughout the study. RESULTS: Seventeen of the 35 patients in the nicotine group had complete remissions, as compared with 9 of the 37 patients in the placebo group (P = 0.03). The patients in the nicotine group had greater improvement in the global clinical grade of colitis (P < 0.001) and the histologic grade (P = 0.03), lower stool frequency (a difference of 1.6 stools daily; P = 0.008), less abdominal pain (P = 0.05), and less fecal urgency (P = 0.009). More patients in the nicotine group had side effects (23, vs. 11 in the placebo group; P = 0.002), the most common of which were nausea, lightheadedness, headache, and sleep disturbance. Withdrawals due to ineffective therapy were more common in the placebo group (3 vs. 8, P = 0.12). CONCLUSIONS: The addition of transdermal nicotine to conventional maintenance therapy improves symptoms in patients with ulcerative colitis.

Administration, Cutaneous↗

Site of production of IGF1 in the normal and stimulated mouse thyroid.

Insulin-like growth factor 1 (IGF1) has emerged as an essential factor in the follicular cell growth response in vitro to TSH, although its source within the thyroid in vivo is not clear. We have studied the localisation of IGF1 mRNA by in situ hybridization using digoxigenin labelled oligoprobes in tissue sections of mouse thyroid. Our results show that in the thyroid IGF1 mRNA is predominantly present in follicular cells and C cells rather than the stroma. Follicular cell levels are higher during postnatal thyroid growth and during the growth response to goitrogen administration, but decrease in the mature animal. This decrease in production is limited to the follicular cells, as IGF1 mRNA is still easily demonstrable in C cells and in the parathyroid. Immunocytochemistry for IGF1 peptide shows a weak and variable follicular cell content in both juvenile and mature mice, but a more uniform distribution during growth in response to a goitrogenic stimulus. These studies show that the follicular cells are the main source of IGF1 in the thyroid, and suggest that the role of IGF1 in follicular cell growth is as an autocrine factor.

Aging↗

Chronic morphologic changes of skeletal muscle ventricles in circulation.

Skeletal muscle ventricles (SMVs) were constructed either extrathoracically or intrathoracically in 44 dogs using the left latissimus dorsi muscle. These SMVs functioned as aortic counterpulsators for from several hours to 216 days. In this study, the relationship between the morphologic changes in the SMVs and their time course in the circulation was evaluated retrospectively. The average volume of the SMV chamber after it had been excised and fixed in formalin was 21.3 +/- 11.0 mL (mean +/- the standard deviation) for extrathoracic SMVs and 20.0 +/- 7.5 mL for intrathoracic SMVs. The volume of the SMV chamber did not correlate with the time course in the circulation. The SMV wall was mainly composed of three components: muscular, fibrous, and fatty aspects. The overall thickness of the wall appeared to be preserved over time in the circulation. However, the thickness of the muscular component tended to decrease over time. SMV rupture occurred in 15 dogs between postoperative days 4 and 39. All ruptures occurred at the suture line between the SMV and the vascular conduits. There was some degree of thrombus in 24 SMVs. Before SMVs can be applied clinically for the purpose of cardiac assist, problems with rupture and thrombus formation must be solved. A better understanding of the morphologic changes that take place in the SMV over time also is needed.

Animals↗

Pericardium-lined skeletal muscle ventricles in circulation up to 589 days.

Skeletal muscle ventricles (SMVs) were constructed from the latissimus dorsi muscle in 15 beagles. The animals were divided into two groups based on modifications in the SMV construction: group I consisted of 5 animals and group II of 10 animals. After a 3-week vascular delay and 6 to 8 weeks of 2-Hz electrical conditioning, the SMVs were connected to the thoracic aorta. In group I, counterpulsation at 33 Hz resulted in an initial 24.4% augmentation of the mean diastolic pressure, a 27.1% decrease in the presystolic pressure, and a 15.9% increase in the endocardial viability ratio. In group II, the mean diastolic pressure rose by 24.7%, the presystolic pressure decreased by 14.3%, and the endocardial viability ratio increased by 24.5%. During propranolol-induced heart failure, the percentage increase in the mean diastolic pressure was improved (12.9% before propranolol infusion versus 27.6% during propranolol infusion), as was the percentage increase in the endocardial viability ratio (11.2% versus 28.7%). Under low cardiac output conditions, SMV contraction resulted in small but statistically significant increases in the total cardiac output (4.3% at 33 Hz, 7.6% at 85 Hz). One animal in group I survived for 589 days with a functioning SMV before progressive dilation of the SMV (impending rupture) developed. Delayed rupture of the SMV sewing ring anastomosis occurred in 2 dogs. Five animals in group II are all alive, with functioning SMVs in the circulation for 377 to 464 days. No animals in group II had rupture of their SMV or showed evidence of thrombus formation.

Animals↗

Cardiomyoplasty: probable mechanism of effectiveness using the pressure-volume relationship.

The mechanism of effectiveness of cardiomyoplasty was evaluated in the setting of chronic left ventricular dysfunction in terms of the pressure-volume relationship. The distal branches of the left coronary artery were ligated in 12 sheep. Seven sheep died and the 5 survivors underwent cardiomyoplasty using a left latissimus dorsi graft 10 to 12 weeks later. These muscle grafts were then electrically conditioned for 2 months. The systemic pressure and cardiac output were not different between the postinfarction and postcardiomyoplasty period with the pacemaker off or on. However, the pressure-volume loops were altered by cardiomyoplasty in all 5 animals. Emax, which is an index of ventricular contractility, increased after cardiomyoplasty from 2.66 +/- 0.92 to 4.59 +/- 1.73 mm Hg/mL (mean +/- the standard deviation; p < 0.05), but did not change between the pacemaker off and on situations. The pressure-volume area, which strongly correlates with myocardial oxygen consumption, decreased after cardiomyoplasty (1,932 +/- 615 mm Hg.mL), compared with before cardiomyoplasty (3,776 +/- 1,201 mm Hg.mL) (p < 0.05), but did not change between pacemaker off and on. The probable mechanism responsible for the effectiveness of cardiomyoplasty is an "active" support or constraint of the damaged myocardium by the latissimus dorsi and the prevention of further ventricular dilation. This suggests that left ventricular systolic function can be augmented by cardiomyoplasty, but that it is a secondary mechanism of action.

Animals↗

Changes caused by processing complete mandibular dentures.

Qualitative and quantitative comparisons were made before and after complete mandibular dentures were processed. Linear measurements indicated shrinkage in all dimensions, and the greatest shrinkage occurred in an anteroposterior direction along the lingual flanges. Differences in shrinkage across the various points measured suggest that the denture material twists during curing, and the final qualitative changes appear as pressure areas in the distolingual and anterolabial regions.

Acrylic Resins↗

Expression of the multidrug resistance-associated protein (MRP) gene in human lung tumours and normal tissue as determined by in situ hybridisation.

In a number of cell lines with a multidrug resistant phenotype, there is no overexpression of the putative efflux pump, P-glycoprotein. Some such lines do, however, overexpress the MRP gene which encodes a protein bearing considerable amino acid homology to P-glycoprotein. We have used in situ hybridisation to study expression of the MRP gene in human cell lines, lung tumours (representing all the major histologies) and normal lung tissue. Considerable heterogeneity of expression was seen in parental cell line COR-L23/P whereas relatively uniform high-level expression was seen in the resistant line COR-L23/R. Normal bronchial epithelium was strongly positive, but the major epithelial component of all eight lung tumours studied showed only a negative to weak signal. However, the leading edge of the tumours consistently produced a more intense signal similar to that in normal epithelium. Areas of lymphocytic infiltrate were more strongly positive than the tumour epithelium. These results suggest that expression of the MRP gene may be a significant factor determining response of lung tumours to chemotherapy, but that considerable caution is needed in the interpretation of expression studies carried out on homogenised tissue biopsies.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Intrathoracic and extrathoracic skeletal muscle ventricles in circulation: left ventricular apex-to-aorta configuration.

Skeletal muscle ventricles (SMVs) were constructed from the latissimus dorsi muscle in 12 dogs. In group I (n = 6), SMVs were placed intrathoracic, in the apex of the left hemithorax. In group II (n = 6), SMVs were positioned extrathoracic between the chest wall and subcutaneous tissue. After a 3-week vascular delay period, SMVs were electrically pre-conditioned with 2-Hz continuous stimulation for 6 weeks. At a second procedure, a valved conduit was placed between the left ventricular (LV) apex and the SMV, and a second valved conduit between the SMV and the thoracic aorta. The SMVs were stimulated to contract during diastole at a 1:2 ratio with the heart. In group I, SMVs generated peak pressures of 91 +/- 10 mmHg, pumped 47% of the systemic blood flow (0.73 +/- 0.25 vs 1.54 +/- 0.42 L/min; p < 0.05), and produced a 25% decrease in the LV systolic tension-time index (TTI) (16.9 +/- 2.7 vs 12.5 +/- 3.3 mmHg.sec; p < 0.05). In group II, SMV peak pressure was 93 +/- 10 mmHg, SMVs pumped 51% of the systemic blood flow (0.78 +/- 0.10 vs 1.53 +/- 0.42 L/min; p < 0.05), and the LV systolic TTI decreased 29% (14.0 +/- 0.8 vs 9.9 +/- 2.0 mmHg.sec; p < 0.05). There was no significant difference between group I and II. These data indicate that the SMV:LV apex-to-aorta configuration is the most effective method reported to date for skeletal muscle cardiac assist. Extrathoracic and intrathoracic SMVs functioned equally well after connection to the circulation.

Anastomosis, Surgical↗

Thickness of adherent mucus gel on colonic mucosa in humans and its relevance to colitis.

The thickness of adherent mucus gel on the surface of colonic mucosa was measured in surgically resected specimens from 46 'control' patients most of whom had carcinoma of the colon; 12 were from right colon, 17 left colon, and 21 from rectum. In addition specimens were examined from 17 patients with ulcerative colitis and 15 patients with Crohn's disease. In controls a continuous layer of mucus was readily seen on specially prepared sections viewed by phase contrast illumination. Mean values for right and left colon and rectum were 107 (48), 134 (68), and 155 (54) microns respectively with a significant difference between right colon and rectum (p = 0.015). Values in ulcerative colitis showed greater variation and in those areas with acute inflammation mucosa was denuded of the mucus layer. In contrast, values for Crohn's disease were normal or greater than normal in thickness--right colon 190 (83) microns compared with 107 48 microns, p = 0.0093. A series of validation experiments are described for the method used to measure mucus thickness. The possible role of mucus in the pathogenesis of inflammatory bowel disease is discussed.

Adolescent↗

Patients with adenomatous polyps and carcinomas have increased colonic mucosal prostaglandin E2.

Colorectal carcinoma in humans and animal models is associated with increased synthesis of prostaglandin E2 (PGE2). PGE2 synthesis was measured in normal and neoplastic human colorectal mucosa to investigate its role in the adenoma-carcinoma sequence. Paired mucosal biopsy specimens for PGE2 synthesis and histological examination were obtained during 39 diagnostic colonoscopies. Twelve control patients in whom colonoscopies and histology were normal synthesised similar amounts of PGE2 at all sites. Their results were (mean (SD) pg PGE2/mg tissue) caecum 102.8 (15.9) (n = 6), ascending colon 110.8 (24.3) (n = 10), transverse colon 103.9 (19.5) (n = 11), descending colon 102.9 (23.2) (n = 12), sigmoid colon 96.4 (18.0) (n = 12), and rectum 107.1 (17.6) (n = 12). Nineteen patients had a total of 27 adenomatous polyps (rectum (1), sigmoid (22), descending (1), transverse (1), and ascending colon (1): histology-tubular (16), tubulo-villous (8), and villous adenomous (3)). The polyps (178.0 (55.0), n = 27) synthesised more PGE2 than controls (p < 0.001), but the values in polyp-associated mucosa (mean (SD) 115.4 (21.9), n = 15) were not different to control results. Eight patients had carcinomas (rectal (2), sigmoid (4), and caecal (2)) all of which were adenocarcinomas. The cancers (193.6 (40.2), n = 8) synthesised more PGE2 than control specimens (p < 0.001), but were not different to polyps. Cancer-associated mucosa (140.3 (27.7) n = 8) synthesised more PGE2 than control and polyp-associated mucosa. Colorectal neoplasia is associated with a progressive increase in PGE2 synthesis which may have a role in tumourigenesis and be a pathophysiological explanation for the beneficial effects of NSAIDs in animal models and human disease.

Adenocarcinoma↗

Synthesis and storage in rat thyroid C-cells.

Thyroid C-cells have the capacity to produce a variety of peptides, as do C-cell tumors. The cellular content of one such peptide, somatostatin, is restricted to a minority of C-cells in rat and human. We set out to clarify whether the synthesis of somatostatin is equally restricted and to study changes that occur in somatostatin synthesis with age. We used immunocytochemistry to localize somatostatin and calcitonin in conjunction with in situ hybridization, using digoxigenin-labeled oligoprobes to localize somatostatin and calcitonin mRNAs in serial sections of formalin-fixed, paraffin-embedded rat thyroid, and correlated peptide and mRNA content in individual cells. All C-cells synthesize and store calcitonin, and somatostatin synthesis, as shown by mRNA content, is limited to the subset of cells containing immunoreactive somatostatin. The numbers of C-cells in general and of the subset synthesizing somatostatin increase between juvenile and adult animals, but the somatostatin cells remain confined to a small area of the gland. These findings support the proposal that somatostatin production is not facultative, but that C-cells differentiate into two distinct subsets of cells, only one of which synthesizes and stores somatostatin.

Aging↗

Removable partial denture design: importance of clinical variables.

A study was conducted to ascertain the influence of clinical variables on removable partial denture design. Dentures were first designed using only the information usually available to technicians, namely, surveyed, articulated study casts. These designs were then modified using information available to the dentist, that is, clinical variables. Of the 208 dentures analysed, 80 (39%) needed modification to 171 components because of patient-related variables. This high number of modifications reinforces the position that removable partial denture design should be instigated and guided by the dentist.

Dental Occlusion, Traumatic↗

Detection of canine allograft lung rejection by pulmonary lymphoscintigraphy.

We previously demonstrated that lymphoscintigraphy could be used to study pulmonary lymphatic flow. Radiocolloids, high-molecular-weight proteins tagged with radioactive markers, are injected percutaneously in the periphery of the lung. These molecules enter the lymph, are transported via lymphatic channels, and concentrate in the tributary hilar and mediastinal lymph nodes, where they can be visualized by nuclear scan. The goal of this study was to determine whether pulmonary lymphoscintigraphy could be used to detect allograft rejection after lung transplantation. Thirteen mongrel dogs underwent left lung allotransplantation. Cyclosporine 15 mg/kg per day and azathioprine 1 mg/kg per day were given orally for postoperative immunosuppression. Lymphoscintigraphic studies were obtained 1 week after the operation and then at weekly intervals. In five dogs (group A), immunosuppression was continued until the animal died or was put to death 6 weeks later. Lymphoscintigraphy demonstrated reestablishment of lymphatic drainage between the lung graft and the mediastinum in all the animals 2 to 4 weeks after transplantation. In eight dogs (group B), immunosuppression was discontinued after reestablishment of graft lymphatic drainage was documented by two consecutive lymphoscintigraphic studies. The dogs continued to be studied with weekly scans. In group B, lymphatic drainage from the lung graft to the mediastinum disappeared 1 to 4 weeks after immunosuppression was stopped. Rejection was diagnosed clinically and confirmed histologically with open lung biopsies and/or autopsies in all animals. This study shows that canine allograft lung rejection is associated with disappearance of lymphatic drainage from lung graft to mediastinum, which can be documented by pulmonary lymphoscintigraphy, a minimally invasive technique that can be easily repeated. Pulmonary lymphoscintigraphy may be useful for early detection of lung allograft rejection.

Acute Disease↗

Metabolite-modulated complex formation between alpha-glycerophosphate dehydrogenase and lactate dehydrogenase.

A modified Hummel-Dreyer equilibrium chromatography technique was used to test the hypothesis that NADH induces the molecular association of lactate dehydrogenase (LDH) and alpha-glycerol-3-phosphate dehydrogenase (alpha-GDH). In the presence of a very limited NADH concentration, a unique elution profile with a new peak running immediately ahead of a trough at the free alpha-GDH elution position is obtained. The appearance of this peak-trough profile is physical evidence that reversible association between LDH and alpha-GDH occurs over a very limited range of free NADH concentrations. The association constant for this complex formation between LDH and alpha-GDH is estimated to be 2.0 microM-1. With the NADH concentration increased to saturation level, no evidence of binding is observed. Such concentration-dependent behavior suggests that the strong competition between LDH and alpha-GDH for the limited amount of NADH tends to promote the enzyme-enzyme contact in order to make the most efficient use of the shared metabolite. The experimental results described in this article make a convincing argument for a metabolite-modulated enzyme-enzyme interaction along this metabolic pathway.

Binding, Competitive↗

Double cardiomyoplasty: acute versus chronic results.

We previously found that double cardiomyoplasty using both acutely raised, unconditioned latissimus dorsi muscles increased cardiac output by 9.6% (1,547 +/- 154 versus 1,695 +/- 166 mL/min), stroke volume by 18.2% (12.1 +/- 0.6 versus 14.3 +/- 0.7 mL), peak left ventricular pressure by 18.4% (98 +/- 3 versus 116 +/- 5 mm Hg), and peak right ventricular pressure by 62.5% (24 +/- 2 versus 39 +/- 4 mm Hg) (p < 0.05 for all differences). In this study 10 dogs underwent double cardiomyoplasty: 3 died perioperatively, and 7 underwent 8 weeks of muscle conditioning. After the conditioning period, the muscle flaps did not contract in 2 of the 7 dogs. Hemodynamics were measured in the remaining 5 dogs. Using fatigue-resistant muscle, cardiac output decreased by 3.7% (1,279 +/- 262 versus 1,233 +/- 274 mL/min), stroke volume decreased by 9.0% (9.5 +/- 1.2 versus 8.8 +/- 1.2 mL), and peak left ventricular pressure increased by 10.6% (82.1 +/- 6.5 versus 90.8 +/- 3.2 mm Hg), but not significantly. Peak right ventricular pressure increased significantly by 31.3% (24.3 +/- 2.1 versus 31.9 +/- 3.6 mm Hg; p < 0.05). Hemodynamic effects of individual left or right muscle contractions versus bilateral muscle stimulation were not significantly different except for a greater percentage increase in peak right ventricular pressure (right, 24.9 +/- 2.1 mm Hg unstimulated versus 28.0 +/- 2.1 stimulated; left, 26.3 +/- 0.9 mm Hg unstimulated versus 30.7 +/- 2.4 mm Hg stimulated; bilateral, 24.3 +/- 2.1 mm Hg unstimulated versus 31.9 +/- 3.4 mm Hg stimulated; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗