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G A Edwards

Publications and source records attributed to G A Edwards.

At least 37 records · Page 2Linked to original sources
PubMed1998

Evaluation of a collagen-based biosynthetic material for the repair of abdominal wall defects.

A collagen tissue polymer composite manufactured in sheep and prepared in two different forms (wet and dry) was compared to polypropylene mesh and to a control group for effectiveness in the repair of an abdominal wall defect in a rabbit model. The wet and dry patches were shown to differ significantly in their pore size. The wet material was shown to retain its natural porosity and promoted neovascularization, tissue integration, cellular infiltration, and neomatrix formation compared to the dry collagen-polymer patch. This material was superior to the polypropylene mesh implant, which was associated with significant adhesions. The appearance of type VI collagen was the earliest sign of new cell infiltration and neomatrix formation within the implant. New deposition of type VI collagen was apparent throughout the thickness of the implant within 4 weeks, followed by type III collagen accumulation. Decreased porosity of the collagen component in the dry patches resulted in a totally nonintegrated implant. This induced a foreign-body capsule with minimal cellular tissue infiltration and no deposition of collagen types VI and III within the implant.

Abdominal Muscles↗
PubMed1998

Association of halofantrine with postprandially derived plasma lipoproteins decreases its clearance relative to administration in the fasted state.

The oral bioavailability of halofantrine (Hf), a highly lipophilic phenanthrenemethanol antimalarial, is significantly enhanced when ingested with food. Although food enhances the absorption of Hf, it also alters the intrinsic pharmacokinetics of Hf as the observed postprandial absolute bioavailability was greater than 100% (Humberstone et al., J. Pharm. Sci. 1996, 85, 525-529). In this study, the association of Hf with plasma lipoproteins and the effect of postprandial lipoproteins on the pharmacokinetics of Hf after intravenous administration was examined in beagles. In fasted dogs, approximately 50% of plasma Hf was associated with lipoproteins, with HDL accounting for 42-43%, LDL for 4-5%, and triglyceride rich lipoproteins (TRL) for 2-3%. At 0.5 and 2 h postdosing in the postprandial state, the proportion of Hf present in both TRL and LDL increased to 7-10%. Changes in Hf distribution between lipoprotein fractions reflected the respective postprandial changes in plasma triglyceride (TG) concentrations. In terms of pharmacokinetics, when an equivalent dose of Hf was administered intravenously in a crossover study to fed and fasted beagles, plasma Hf AUC values were significantly higher, and CL and Vss were significantly lower, in the fed state compared to the fasted state (p < 0.05). The mean postprandial increase in plasma AUC values was 19% (range 14-34%), with corresponding decreases in CL (15%) and Vss (21%). A broadly linear relationship between increased postprandial Hf concentrations at specific time points (fed vs fasted) and corresponding postprandial increases in TG concentrations suggested that the decreased postprandial clearance of Hf was a function of increased association with TG-rich plasma lipoproteins. This study confirms that the clearance of Hf is influenced by plasma lipoprotein profiles, and the findings have implications for the design and interpretation of fed/fasted bioavailability studies of lipophilic drugs and determination of their intrinsic pharmacokinetic parameters in subjects or patients with dyslipidemic profiles.

Animals↗
PubMed1998

Metabolism of halofantrine to its equipotent metabolite, desbutylhalofantrine, is decreased when orally administered with ketoconazole.

Halofantrine (Hf) is a highly lipophilic antimalarial with poor and erratic absorption. Published data indicates that the oral bioavailability of Hf was increased 3-fold in humans and 12-fold in dogs when administered postprandially; however, the proportional formation of the active desbutyl metabolite (desbutylhalofantrine, Hfm) decreased 2.4-fold in humans and 6.8-fold in dogs (Milton et al., Br. J. Clin. Pharmacol. 1989, 28, 71-77; Humberstone et al., J. Pharm. Sci. 1996, 85, 525-529). The current study was undertaken to confirm the putative involvement of CYP3A4 in the N-dealkylation of Hf to Hfm by administering Hf with and without ketoconazole (KC), a specific CYP3A4 inhibitor, and measuring the resulting plasma concentration profiles of Hf and Hfm. The plasma Hfm/Hf AUC(0-72 h) ratio after fasted oral administration of Hf without KC was 0.56, whereas the ratio after fasted oral administration with KC was less than 0.05. It is likely that both hepatic and prehepatic (enterocyte-based) CYP3A4 contributed to metabolism of Hf to Hfm after oral administration. Interestingly, the low plasma Hfm/Hf AUC ratios observed after fasted administration of Hf with KC were similar to the low values previously observed when Hf was administered postprandially (despite increased Hf absorption). The mechanism(s) by which postprandial administration of Hf led to a decrease in its metabolism are unknown, but based on the current data, could include inhibition of CYP3A4-mediated metabolism by components of the ingested meal. Other possibilities include a lipid-induced postprandial recruitment of intestinal lymphatic transport or avoidance of metabolism during transport through the enterocyte into the portal blood. Further studies are required to determine the relative contributions by which these different processes may decrease the presystemic metabolism of Hf.

Administration, Oral↗
PubMed1997

In vivo evaluation of a collagenous membrane as an absorbable adhesion barrier.

An absorbable membrane made from purified, pepsin-soluble collagen was compared to Interceed, an absorbable cellulose-based product, and to a control group for effectiveness in inhibiting the formation of adhesions between peritoneal surface injuries in adult rats. An adhesion scoring system was used to evaluate and compare the performance of the test materials with the control group in regard to the extent, tenacity, and type of any adhesions evident at 28 days following surgery. The collagen group performed significantly better (p < 0.05) than either the Interceed or control groups, showing fewer, less extensive adhesions. The collagen membranes resulted in either no or weak adhesions between the body wall and caecum. Adhesions in the Interceed group were quite variable and characterized by a marked peritoneal reaction in the caecal and body walls adjacent to adhesions. Control samples were characterized by close, dense fibrotic adhesions between the caecum and body wall. Both of the test materials showed some deficiencies in respect to their physical and handling properties that could be further improved for this indication.

Absorption↗
PubMed1995

Early performance appraisal of the Omniflow II Vascular Prosthesis as an indicator of long-term function.

The search for the ideal vascular prosthesis for below the knee replacement or coronary surgery continues. Long-term explant analysis of a biosynthetic composite vessel, the Omniflow Vascular Prosthesis I, has previously shown sound structural durability. An important determinant in defining durability has been the evaluation of the degree of persistence of the original biological components and the augmentation by new tissue. The development of a panel of specific monoclonal antibodies to collagens, that allow detection of new host collagen among the original collagens of the prosthesis has been a key factor. In the present study, these antibodies have been used to investigate the degree and rate of new collagen tissue infiltration in an improved version of the Omniflow prosthesis. The data show that new collagen types III and VI can be detected as early as 3 months in the adventitial tissue, and that complete tissue augmentation throughout the entire vessel wall is apparent by 6 months after implant. The novel explant analyses serve as a good predictive indication to the in vivo performance of the device and would be useful in rapid monitoring of further modifications to this vessel or to other collagen-based prostheses.

Animals↗
PubMed1995

Business modeling tools for managing decision support systems.

We sought to investigate the role of business modeling tools in facilitating the implementation of interactive decision support systems (DSS) for laboratory test ordering. We have recently shown that Ripple Down Rules (RDR), a new strategy for building expert systems (ES), enables institutions to build DSS maintained by local experts without knowledge engineering support. While DSS hold great promise for improving health outcomes by providing doctors with timely access to care guidelines, implementation will require careful planning and change management. The Situated, Strategic, and AI-Enhanced method was used to define and assess a DSS-driven process change. DECmodelTM, a graphical business modeling application, was used to build representations of current (paper-based) and future (ES-supported) test ordering environments. Models described both the interactions between new processes and the impact on healthcare quality of ES-supported DSS. Models were able to represent the key processes involved in test ordering and the impact of DSS. Users could interact with the model to examine the time and cost implications of the transition from current to future states. The level of detail in which processes could be examined was readily controlled by the user. We have shown that graphical business modeling applications are useful tools for enabling institutions to view the impact of DSS. Accuracy of models should be maximized in workshops involving key management personnel. Whilst the impact of modeling on the cost and quality of DSS implementation remains to be established, we believe these tools are valuable for institutions planning to align DSS technologies to their service needs.

Australia↗
PubMed1994

Psychiatric treatment and services in Australia, 1914-1994.

Eighty years ago, psychiatrists believed that mental illnesses were caused by, among other things, excessive devotion to sport, the introduction of phones and motor cars, ill-sorted marriages and perverted sexual intercourse. Psychiatric theories and institutions in Australia have come a long way since then.

Australia↗
PubMed1993

Structural analysis of a collagen--polyester composite vascular prosthesis.

The Omniflow Vascular Prosthesis is a collagen--polyester composite which has been used successfully for peripheral vascular replacement. In this study, we have examined the distribution of the various connective tissue components and the ultrastructural organisation of these in order to understand and allow improvement of its functional properties. Using immunohistology with specific monoclonal antibodies, types I and III collagens were found to be the major components throughout the prosthesis. Type VI collagen was also present but was mainly associated with cells, particularly around the polyester mesh and silicone interfaces. While elastin was absent, two elastic tissue microfibrillar proteins were present uniformly throughout the structure. Ultrastructurally, clear differences existed between the local environments of the inner surface, which had formed around the silicone mandrel, the polyester mesh within the prosthesis, and the outer collagenous tissue which formed the central wall. At the inner surface, the amount of collagen was less and the orientation of these fibres was not well defined. The collagen fibrils in the polyester region were smaller than those of the main wall, which were well ordered and orientated along the axis of the device.

Antibodies, Monoclonal↗
PubMed1993

Laboratory diagnosis of phaeochromocytoma: which analytes should we measure?

There is a diversity of advice in the literature as to which biochemical assays are best suited to the investigation of patients with a suspected phaeochromocytoma. The challenge for the clinical laboratory is to select those assays which detect all phaeochromocytomas, whilst having the lowest incidence of false positive diagnoses. We compared the sensitivity and specificity of a wide range of assays currently used for the biochemical diagnosis of phaeochromocytoma using either specific gas chromatographic-mass spectrometric (GC/MS) or high performance liquid chromatography-electrochemical detection (HPLC/ED) techniques. Noradrenaline (NA), adrenaline (ADR), dopamine (DA), 3,4-dihydroxyphenylglycol (DHPG), hydroxymethoxymandelic acid (HMMA), normetanephrine (NMET) and metanephrine (MET) were measured in 24 h urine specimens from 20 patients with histologically proven phaeochromocytoma and a large group of patients referred for investigation but subsequently found not to have a phaeochromocytoma. Because phaeochromocytomas are a heterogeneous group of hormone secreting tumours, no single analyte could achieve 100% sensitivity; 100% sensitivity was achieved only when the combination of both NA and ADR or NMET and MET was used. DA, DHPG and HMMA all had poor sensitivities. HMMA had a sensitivity of 70% when using the upper 95% confidence level (48 mumol/24 h) of the non-tumour patients as the cut-off. By lowering the cut-off to 35 mumol/24 h the sensitivity could be increased to 100% but at the expense of the specificity which was decreased from 98 to 92%. On the basis of this study we recommend the specific measurement of either NA and ADR or NMET and MET as the most suitable analytes for the detection of phaeochromocytoma, and further that, due to its poor specificity, HMMA be abandoned as a suitable analyte.

Adrenal Gland Neoplasms↗
PubMed1992

The impact of recent advances in diagnostic technology on the clinical presentation of phaeochromocytoma.

OBJECTIVE: To examine the impact of recent advances in diagnostic technology on the spectrum of clinical and biochemical features of patients presenting with a new diagnosis of phaeochromocytoma. DESIGN: A retrospective review of the clinical and biochemical features of patients diagnosed by our laboratory as having phaeochromocytoma within a 27-month period up to December, 1990. Noradrenaline, adrenaline and dihydroxyphenylglycol were assayed in 24-hour urine specimens (19 patients) or plasma (1 anuric patient) by gas chromatography/mass spectrometry. SETTING: A tertiary level chemical pathology department. PATIENTS: Twenty patients with a new diagnosis of phaeochromocytoma. RESULTS: The classic, episodic adrenergic symptoms traditionally associated with phaeochromocytoma were absent in 9 of the 20 patients (45%). "Atypical" phaeochromocytoma presented as a mass on computed tomography imaging (6 patients, 30%), "phaeochromocytoma crisis" (4 patients, 20%) or family screening (1 patient, 5%). Excessive adrenaline production was found in 11 patients (55%) and six (30%) had predominantly adrenaline-secreting tumours. The urinary noradrenaline:dihydroxyphenylglycol ratio was raised in all nine patients with predominantly noradrenaline-secreting tumours but was not raised in nine out of ten patients with adrenaline-secreting phaeochromocytoma. Adrenaline excretion was significantly correlated with tumour size (r = 0.8; P less than 0.05). CONCLUSIONS: Advances in diagnostic technology, particularly specific adrenaline assays and computed tomography, have made possible the early diagnosis of patients with phaeochromocytoma presenting in ways previously thought to be uncommon. All patients with adrenal masses noted incidentally on CT scan should be investigated for phaeochromocytoma. Adrenaline-secreting tumours are common and both noradrenaline and adrenaline should be assayed in all patients investigated for phaeochromocytoma.

Adrenal Gland Neoplasms↗
PubMed1992

Development of an ovine collagen-based composite biosynthetic vascular prosthesis.

The search for an ideal vascular prosthesis to bypass peripheral vascular obstructive lesions is necessary where autologous tissues are either unavailable or unsuitable. This paper will outline the development and use of vascular conduits, principally of biological origin. The clinical benefits and limitations of these materials are discussed. The development of a composite biosynthetic prosthesis (Omniflow¿) is described, together with the testing methods used to determine and predict its suitability for use as an arterial substitute. The ovine biosynthetic prosthesis has significantly improved surface and mural properties over previous attempts at producing prostheses for vascular reconstruction. Immunohistological studies on samples recovered from dogs after 4 years show that the original ovine collagen is still present after 4 years, and it is further augmented by the deposition of new, host-derived connective tissue.

Animals↗
PubMed1992

Activation of P1- and P2Y-purinoceptors by ADP-ribose in the guinea-pig taenia coli, but not of P2X-purinoceptors in the vas deferens.

1. The activity of adenosine 5'-diphosphoribose (ADP-ribose), a ribosylated purine nucleotide, was investigated on the carbachol-contracted taenia coli, a tissue possessing P1- (A2) and P2Y-purinoceptors and on the guinea-pig vas deferens which possesses P2X-purinoceptors. 2. In the vas deferens, where ATP (1 microM-1 mM) produced concentration-dependent contractions, ADP-ribose was without effect at concentrations up to 1 mM. 3. In the taenia coli, ADP-ribose (0.1 microM-1 mM) produced concentration-dependent relaxations with a potency similar to that of adenosine, but less than that of ATP. The pD2 values for ADP-ribose, adenosine and ATP were 4.5 +/- 0.07 (27), 4.4 +/- 0.10 (9) and 5.5 +/- 0.14 (21), respectively. The time-course of the relaxations elicited by ADP-ribose was found to be significantly longer than that for ATP and significantly shorter than that for adenosine. 4. The P1-purinoceptor antagonist, 8-phenyltheophylline (5 microM), produced parallel rightward shifts in the concentration-response curves of the relaxations of the taenia coli elicited by ADP-ribose and adenosine but not ATP. 5. Dipyridamole (0.3 microM), a purine nucleoside uptake inhibitor, potentiated the responses to adenosine and ADP-ribose in the taenia coli. These potentiations were sensitive to 8-phenyltheophylline (5 microM). 6. Reactive blue 2, a P2Y-purinoceptor antagonist, antagonized the inhibitory responses of ADP-ribose and ATP in the taenia coli, without significantly altering the inhibitory responses of either adenosine or noradrenaline.7. In the presence of the potassium channel blocker, apamin (0.3 microM), the inhibitory responses of ADP-ribose were severely attenuated, and the inhibitory responses of ATP in the taenia coli were converted to transient contractions. Further addition of 8-PT blocked the residual responses of ADPribose.8. The P2-purinoceptor antagonist, suramin (500 microM), antagonized responses to ATP and ADP-ribose,but not adenosine. Further addition of 8-PT antagonized the residual responses to ADP-ribose, but not to ATP.9. It is concluded that ADP-ribose has a mixed pharmacological profile, evoking both PI (A2)-purinoceptor-mediated responses and P2Y-purinoceptor-mediated responses, while being inert at P2Xpurinoceptors.It is suggested that ADP-ribose may provide a useful starting point for the generation of structural analogues which have specific activity at the P2Y-purinoceptor.

Adenosine Diphosphate Ribose↗
PubMed1991

Pea lectin is correctly processed, stable and active in leaves of transgenic potato plants.

A gene encoding the preproprotein of the pea (Pisum sativum) lectin was expressed in transgenic potato plants using a cauliflower mosaic virus (CaMV) 35S promoter or a tobacco ribulose bisphosphate carboxylase small subunit (ssRubisco) promoter. Presence of the pea lectin to levels greater than 1% of total soluble leaf protein was detected by radioimmunoassay (RIA). The pattern of expression derived from the two promoters was established using both RIA and a squash-blot immunolocalisation technique. Western blotting demonstrated that the preproprotein was correctly processed, generating alpha and beta subunits that assembled to give an isolectin form observed in pea seeds and roots. It was also found that the haemagglutination activity and specificity of pea lectin synthesised in transgenic potato leaves was comparable to purified lectin from pea cotyledons.

Animals↗
PubMed1991

Evaluation of three theophylline dosing methods in pediatric patients.

Three methods used for individualizing theophylline dosing were prospectively evaluated in 34 pediatric patients to compare the methods' ability to accurately predict steady-state serum theophylline concentrations (STCs) from non-steady-state data. Methods evaluated included a Bayesian weighted sum of squares regression program, an algebraic method developed by Chiou, and a commonly used population-based pediatric dosing algorithm. An expanded retrospective evaluation was also done to further compare the Bayesian and Chiou methods. Patients (aged 1-11 y) admitted to the hospital for acute bronchospasm refractory to inhaled beta agonists and with physician's orders to receive intravenous aminophylline were eligible for participation. Study patients received a 6-mg/kg loading dose aminophylline, followed by a 0.8-1.0 mg/kg/h constant aminophylline infusion. STCs were obtained 0.5 and 5.5 hours postinfusion. Subjects were randomized to one of three dosing method groups (Bayesian, Chiou, or pediatric algorithm). Doses were calculated using the assigned method to attain a target steady-state STC. Predictions from each dosing method were compared with actual serum concentrations for bias and precision. Additionally, analysis of fit-to-the-line-of-identity for predicted versus observed STCs was evaluated for each method. Precision of methods was also compared with regard to their ability to predict within 20 percent of their observed steady-state STC. Results from the prospective evaluation showed no significant difference between the three methods tested. Predicted STCs fell within 20 percent of their observed steady-state concentrations for 18 percent (2/11) of patients in the algorithm group, and 45 percent (5/11) of patients in the Chiou group and 17 percent (2/12) of the patients in the Bayesian group met this criterion. Retrospective analysis of all 34 patients demonstrated that the Bayesian and Chiou methods had similar bias and precision and no statistical difference was found between them. The results from this evaluation suggest that the pediatric dosing algorithm is equivalent in predictive bias and precision to the Bayesian and Chiou methods as well as in its ability to identify doses that result in steady-state STCs within 20 percent of their target values. Given the relative inaccuracy of these methods, cautious use of these techniques is recommended when evaluating non-steady-state STCs obtained from children during the acute stages of reactive airway disease.

Algorithms↗
PubMed1991

Structural stability of long-term implants of a collagen-based vascular prosthesis.

Samples of an ovine collagen-polyester composite device suitable for peripheral revascularization, the Omniflow Vascular Prosthesis, have been retrieved for morphological and immunohistological analyses during and up to 4 years of implantation in a dog aortoiliac by-pass model. At the various sample times, the prosthesis explants were shown to retain their structural integrity, with no aneurysm formation and with little thrombus accumulation. Immunohistological studies on samples of the prosthesis showed that the original ovine collagen was still present after 4 years, and that there had been augmentation by the deposition of new, host-derived connective tissue.

Animals↗
PubMed1987

Renal handling of phosphate following release of ureteral obstruction.

The handling of phosphate by the kidney following release of unilateral ureteral obstruction (UUO) was investigated in intact and thyroparathyroidectomized (TPTX) dogs, and compared to that in the kidney following unilateral release of bilateral ureteral obstruction (BUO). By contrast to the kidney after release of BUO, the kidney following release of UUO showed a much lower fractional excretion (FE) of phosphate in TPTX animals (BUO 21.5 +/- 6.8%; UUO 1.3 +/- 0.5%) and a blunted phosphaturic response to PTH (BUO delta + 25.8%; UUO delta + 2.6%). Administration of cyclic AMP, prostaglandin synthetase inhibitors and ammonium chloride failed to correct the hypophosphaturia or the blunted response to PTH. Raising the filtered load of phosphate, however, raised the FE of phosphate in TPTX dogs in the kidney after release of UUO to levels comparable to those in BUO (BUO 21.5 +/- 6.8%; UUO 21.8 +/- 5.1%) and restored the responsiveness to PTH (BUO 49.0 +/- 8.2%; UUO 39.7 +/- 10%). When reabsorptive capacity (RC) was calculated during stepwise increments of serum phosphate, an additional difference was identified between the kidney after release of UUO on the one hand, and the control kidney and the kidney after release of BUO on the other: RC for phosphate was 294 +/- 66 micrograms/min . kg in UUO, 130 +/- 16 micrograms/min . kg in control, and 62 +/- 19 micrograms/min . kg in BUO. It is concluded that, in addition to the role of reduced filtered load of phosphate, an increased capacity to reabsorb phosphate is responsible in part for the hypophosphaturia observed in the kidney following release of UUO.

Ammonium Chloride↗