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Biomedical subjects

M C Stacey

Publications and source records attributed to M C Stacey.

At least 37 records · Page 2Linked to original sources

Acetylation phenotype and cytochrome P450IA2 phenotype are unlikely to be associated with peripheral arterial disease.

The hypothesis that cytochrome P450IA2 (CYPIA2) and/or N-acetyltransferase 2 (NAT2) may be involved in the pathogenesis of peripheral arterial disease was investigated in 90 Australian patients with significant disease and 81 matched control subjects. CYPIA2 and NAT2 phenotypes were determined from urinary metabolite patterns after an oral dose of caffeine. NAT2 phenotype was similar (chi 2 = 0.01; p = 0.98) in both atherosclerotic patients (43.3% rapid) and control subjects (42.0% rapid). CYPIA2 metabolism as measured by the median ratio of (1,7-dimethylxanthine + 1,7-dimethyluric acid)/caffeine was significantly induced by smoking in both patients with atherosclerosis (ratio of 6.5 in nonsmokers and 12.4 in smokers; p < 0.05) and control subjects (ratio of 8.2 in nonsmokers and 14.8 in smokers; p < 0.05), but values in atherosclerotic and control nonsmokers and smokers were similar. Probit transformation of the data revealed a trimodal distribution of ratios in control subjects who were nonsmokers, with 5% classified as poor metabolizers (homozygous rapid) and 95% as extensive metabolizers. The distribution of ratios in control subjects who were smokers was unimodal, whereas among the patients with arterial disease, both smokers and nonsmokers exhibited a bimodal pattern with 8.2% to 16% poor metabolizer and 84% to 91.8% extensive metabolizer phenotypes. When data from both nonsmokers and smokers were combined, the overall proportion of subjects who were poor metabolizers was not significantly different (chi 2 = 1.82; p = 0.18) between control subjects (3.8%) and patients with atherosclerosis (10.6%). Thus biotransformation of environmental or dietary aromatic or heterocyclic amines by NAT2 or CYPIA2 is unlikely to have a significant role in the cause or pathogenesis of peripheral arterial disease.

Acetylation↗

General practitioners' attitudes to computer-generated surgical discharge letters. Members of the Department of General Surgery, Fremantle Hospital.

OBJECTIVE: To assess general practitioners' attitudes to a computed-generated general surgical discharge letter. To identify the six most important items of information in an ideal discharge letter. DESIGN: One hundred and thirty general practitioners who had received at least six computer-generated surgical discharge letters in one year were circulated with a questionnaire. RESULTS: Most general practitioners approved of the computer-generated discharge letter which included all six of the most important items of information they requested. Eighty-four per cent wished to see a similar computer-generated discharge system extended into other areas of hospital practice.

Attitude of Health Personnel↗

Aetiology of chronic leg ulcers.

This study was undertaken to determine the relative prevalence of the factors causing chronic ulceration of the leg in the general population. Two hundred and fifty-nine patients with chronic ulceration of the leg were found on screening a Western Australian population of 238,000. (The prevalence of chronic ulceration of the leg was 1.1 per 1000 population.) Two hundred and forty-two of these patients (93%) with 286 chronically ulcerated limbs were fully assessed to determine the factors contributing to ulceration. In 239 limbs (84%) ulceration involved the leg; in these limbs venous disease was the most prevalent cause of ulceration (160 limbs). Arterial disease was found in 66 limbs, with both venous and arterial disease present in 35 limbs. Rheumatoid arthritis was a causative factor in 27 limbs and diabetes was found with 29 limbs with ulceration involving the leg. In 47 limbs (16%) ulceration was confined to the foot; arterial disease (35 limbs) and diabetes (23 limbs) were the most prevalent causes of ulceration in these limbs. Venous disease was infrequent (three limbs). No disorder of the circulation was found in 48 limbs (20%) with ulceration involving the leg, and in 58 (20%) of all ulcerated limbs. More than one aetiological factor was present in 93 limbs (33%). A cause for ulceration was not found in 10 limbs (3.5%).

Adult↗

The effect of bacterial colonization on venous ulcer healing.

To determine the effect of bacterial colonization on venous ulcer healing, 82 patients with 100 venous ulcerated limbs were each studied prospectively for six months. Despite bacteriological swab results, topical or systemic antibiotics were not administered unless cellulitis supervened. Initial ulcer size, length of ulcer history and time to complete healing of colonized and uncolonized ulcers were determined and compared. Organisms were cultured from 83 limbs prior to commencement of treatment, the commonest isolates being Staphylococcus aureaus (48%), mixed coliforms (28%), Pseudomonas aeruginosa (21%) and anaerobes (17%). When compared with ulcers with no bacterial growth, colonized ulcers were of longer duration (p [symbol: see text] 0.01), had a larger initial size (p [symbol: see text] 0.001) and had significantly longer healing time (p [symbol: see text] 0.001). When analysed individually beta-haemolytic streptococci, anaerobes, Staphylococcus aureus and coliforms were associated with delayed healing. Delayed healing was not found with Pseudomonas aeruginosa, although pseudomonas-colonized ulcers were significantly larger and of longer duration than uncolonized ulcers. Bacterial colonization is associated with delayed venous ulcer healing. To further clarify the pathogenicity of colonizing bacteria, however, the effect of their eradiction on healing of venous ulcers needs to be established.

Adult↗

How accurate is a computerized surgical audit when resident medical staff collect the data?

Since July 1988 all eight general surgeons at Fremantle Hospital have used a computer-based surgical audit and discharge system. At the time of writing (September 1991) 10,919 computer-generated discharge letters have been produced by the system. This paper describes the system and reports a series of quality control assessments carried out between 1 July 1988 and 30 June 1990 during which 30 pre-registration surgical residents completed 5,716 data collection forms. It was found that: (1) data collection for 23 of 24 monthly surgical audits was at least 95% complete; (2) outstanding surgical discharge summaries were reduced by 89%; (3) the residents recorded 17/19 wound infections and identified 15 (79%) of these as a surgical complication; and (4) the residents tended to under-record complications in patients who had more than one complication during their hospital stay. It was concluded that the system was robust, and that resident staff collected data in such a way that good quality computer-generated discharge letters were produced in a timely manner. Closer attention to aspects of data collection will be required before the optimum surgical audits of the QX system can be generated.

Abstracting and Indexing↗

Epidemiology of chronic venous ulcers.

A metropolitan population of 238,000 in Perth, Western Australia, was screened for chronic ulceration of the leg. Patients with a chronic leg ulcer and a venous abnormality comprised 57 per cent of all patients with a chronic leg ulcer, giving a prevalence of 0.62 per 1000 population. There was an increasing prevalence with age; 90 per cent of patients were 60 years and older. This group comprised 16.7 per cent of the population, and had a prevalence of 3.3 per 1000. Although chronic venous ulcers were more common in women there was no difference in age related prevalence. In 36 per cent of patients with a venous abnormality, there was at least one other aetiological factor contributing to chronic ulceration of the leg; 96 per cent had either a history of deep venous thrombosis or a condition known to predispose to deep venous thrombosis.

Adult↗

Influence of phlebographic abnormalities on the natural history of venous ulceration.

Eighty-five limbs in 73 patients with a healed venous ulcer were assessed by ascending and descending phlebography, foot volume plethysmography and transcutaneous oxygen measurements. Forty-four limbs had post-thrombotic changes on ascending phlebography. In 24 (28 per cent) these extended into the femoral vein, while in 20 (24 per cent) only the calf veins were involved. In the 41 limbs (48 per cent) with normal deep veins on ascending phlebography, 11 had evidence of localized incompetence of the calf communicating veins, 14 had either long saphenous incompetence, deep vein reflux to the level of the knee or below, or both of these abnormalities, and 16 limbs had no phlebographic abnormalities. However all limbs had a decreased half volume refilling time on foot volume plethysmography. Limbs with post-thrombotic changes extending into the femoral vein were associated with a significantly longer history of ulceration and more ulcer recurrences than limbs with calf vein damage (P less than 0.05 for each) and limbs with normal deep veins (P less than 0.01 for each). However, these limbs did not have lower transcutaneous oxygen ratios or longer times to achieve ulcer healing. Ascending phlebography identified a group of limbs with extensive post-thrombotic changes in which there was a higher incidence of ulcer breakdown, but this was not associated with a delay in ulcer healing.

Adult↗

Outpatient treatment of chronic venous ulcers in a specialized clinic.

Chronic leg ulcers have many different causes and therefore need an accurate diagnosis in order to give the most effective treatment. A specialized clinic was set up in Fremantle Hospital in July 1988 with the aims of performing a thorough clinical and laboratory assessment to establish the cause of ulceration in every patient, and treating patients according to the cause of ulceration. Patients with arterial, neoplastic or dermatological conditions were treated as appropriate for their diagnosis and patients with other chronic ulcers were managed as outpatients where possible. Patients were seen between July 1988 and July 1989. Only 43% had purely venous ulcers, 32.6% had a venous component plus some other abnormality, and 5.2% were purely arterial. Using an outpatient treatment regimen, 67% of all ulcerated limbs and 73.7% of limbs with purely venous ulcers were healed within 6 months. Only 11 patients with venous ulceration (15 limbs) failed on this therapy and required admission during the observation period. The initial ulcer size was shown to influence the time to total healing of the limb. The healing rates achieved compare favourably with studies from other specialized centres and suggest that the majority of patients with chronic leg ulcers can be treated successfully using ambulatory outpatient dressing techniques.

Adult↗

Measurement of the healing of venous ulcers.

The surface area of 99 leg ulcers was measured from a scaled photograph using a computerized ultrasonic digitizer. This was compared with the area obtained by multiplying the two maximal perpendicular diameters of each ulcer. There was an extremely good correlation between these two methods (r = 0.951). Seventy-four patients were followed up as part of a placebo-controlled double-blind study. In this study, treatment was assessed by the time taken for the ulcerated limb to heal completely. The initial ulcer size was found to be a weak predictor of subsequent ulcer healing (r = 0.49). The healing rates of individual ulcers calculated over 1 month intervals from presentation proved to be a poor predictor of the time required for complete ulcer healing (Spearman rank correlation coefficients ranged from 0.15 to 0.61). The healing curves of individual ulcers showed considerable fluctuations during the process of healing. The product of the maximal dimensions of an ulcer provides an easy and accurate method of monitoring treatment. The reduction in ulcer size within a set time interval, used in many ulcer studies, is a poor predictor of eventual ulcer healing. The percentage of ulcers completely healed within a pre-determined time interval is a better method of assessing new treatments.

Adult↗

Transcutaneous oxygen tensions in assessing the treatment of healed venous ulcers.

Transcutaneous oxygen tension (Ptc,O2) was assessed as an indicator of risk of reulceration in 68 limbs with healed venous ulcers. Ptc,O2 was also used to assess two methods of ulcer prophylaxis. Measurements were made over the gaiter skin, the healed ulcer and the upper arm. The results were expressed as a ratio of the lower limb readings over those taken from the arm. Patients were randomized, after the ulcer had healed, to elastic stockings and stanozolol, or elastic stockings and surgical ligation of incompetent superficial veins. Patients who declined to participate in the study were prescribed elastic stockings only. Those limbs remaining healed at 12 months had Ptc,O2 ratios remeasured. The Ptc,O2 ratios from limbs that reulcerated were not significantly lower than those from limbs remaining healed. The Ptc,O2 ratio was significantly increased in limbs treated by stanozolol and elastic stockings (P less than 0.05) and by surgery and elastic stockings (P less than 0.05). There was no significant increase in Ptc,O2 in limbs treated by elastic stockings alone. In those treated by surgery and elastic stockings, there was a significant improvement in limbs with normal deep veins (P less than 0.01), but not in limbs with post-thrombotic changes on ascending phlebography. Although these two methods of ulcer prophylaxis improve the Ptc,O2 ratio, a high ratio has not been shown to be beneficial in preventing ulcer recurrence.

Adult↗

Calf pump function in patients with healed venous ulcers is not improved by surgery to the communicating veins or by elastic stockings.

Calf muscle pump function was assessed in 41 limbs after venous ulcers had healed. Treatment was then randomized either to ligation of incompetent lower leg communicating veins and ablation of incompetent superficial veins combined with permanent graduated compression elastic stockings, or to graduated compression elastic stockings only. Half volume refilling time (TV1/2) and relative expelled volume (EVrel) measured on foot volume plethysmography were used to assess calf muscle pump function. This was repeated after 12 months. The initial TV1/2 and EVrel were significantly lower than for normal limbs. There was no significant improvement in TV1/2 in either treatment group (Student's t test, P = 0.78, P = 0.19). EVrel did not improve significantly in limbs treated with elastic stockings alone (P = 0.94), but there was a slight but significant improvement in EVrel in limbs treated with surgery and elastic stockings (P = 0.048); however, this was still significantly below the normal range (P less than 0.001). In limbs without phlebographic evidence of post-thrombotic changes, treated with the combination of surgery and elastic stockings, there was a significant improvement in EVrel (P = 0.035), but no improvement was found in limbs with post-thrombotic changes. This small but significant improvement in EVrel in limbs without post-thrombotic changes treated by surgery and elastic stockings may explain the reduced incidence of reulceration that has been found following surgical eradication of the superficial and communicating veins.

Adult↗

Changes in the apparently normal limb in unilateral venous ulceration.

Forty-seven patients with unilateral venous ulceration have been investigated to determine if any abnormalities were present in the contralateral limbs which had not had lipodermatosclerosis or ulceration. Ascending phlebography in the non-ulcerated limbs showed post-thrombotic changes in 28 per cent and incompetent lower leg communicating veins in 19 per cent. This incidence was not significantly different to the limbs with healed ulceration (45 and 23 per cent respectively, chi 2 test, P = 0.10). Half volume refilling time measured by foot volumetry suggested that 79 per cent of the non-ulcerated limbs had evidence of deep vein incompetence or incompetent lower leg communicating veins, which was again similar to the incidence in the previously ulcerated limbs (85 per cent). Transcutaneous oxygen readings, expressed as a ratio of a reading at a standard site in the gaiter region of the leg over a reading from the upper arm, were significantly lower in non-ulcerated limbs (mean 0.84 +/- 0.26 s.d.) than in a cohort of age and sex matched controls (mean 1.02 +/- 0.14, Student's t test, P less than 0.001), and significantly higher than in previously ulcerated limbs (mean 0.68 +/- 0.31, P less than 0.01). Abnormalities in venous anatomy and function have been shown, in conjunction with evidence of reduced oxygen diffusion, through the gaiter skin before overt skin changes develop.

Adult↗

Beta-adrenergic blockade and peripheral vascular disease.

Hypertension and ischaemic heart disease are common accompaniments of peripheral vascular disease, and are often treated with beta-blocking drugs. Previous reports, however, have suggested that these drugs may aggravate peripheral vascular disease. A study was designed to investigate this problem with claudication-distance and skin and muscle blood-flow studies (as determined by 133Xe clearance) as indices for assessment. In all 11 patients who presented with features of peripheral vascular disease and were found to be taking beta-blocking drugs, administration of the drug was stopped, blood pressure was controlled by other means, and the situation was reassessed four weeks later. There was a significant improvement in claudication distance and in resting and post-exercise muscle blood flow after withdrawal of the drug. This held for both cardioselective and nonselective beta-blockers. It is recommended that this group of drugs be avoided in the treatment of patients with peripheral vascular disease.

Adrenergic beta-Antagonists↗

Biochemical analysis of wound fluid from nonhealing and healing chronic leg ulcers.

The purpose of this study was to determine the biochemical composition of fluid taken from chronic wounds, to compare these values with that of serum, and therefore to assess whether the wound fluid is representative of the extracellular environment of the wound. Paired wound fluid and blood samples were collected from eight patients with chronic leg ulcers in a nonhealing and healing phase. Wound fluid and serum samples were screened for a profile of general biochemical analyses, including electrolytes, lactate, glucose, and protein analyses. Electrolyte levels were essentially identical in wound fluid and serum samples. Lactate and lactate dehydrogenase levels were significantly greater and glucose and bicarbonate levels were significantly lower in wound fluid when compared with the paired serum samples. Albumin and total protein levels in wound fluid were on average half those of serum levels. In this small sample of eight patients, wound fluid collected from chronic leg ulcers is an exudate with the biochemical composition expected in extracellular fluid. In addition, bicarbonate and glucose levels increase and C-reactive protein levels decrease in wound fluid, but remain unchanged in serum, during healing. These results suggest changes in the state of hypoxia and the inflammatory process in the healing wound.

Journal Article↗

Analysis of the acute and chronic wound environments: the role of proteases and their inhibitors.

To assess the differences in proteolytic activity of acute and chronic wound environments, wound fluids were collected from acute surgical wounds (22 samples) and chronic wounds (25 samples) of various etiologies, including mixed vessel disease ulcers, decubiti and diabetic foot ulcers. Matrix metalloproteinase (MMP) activity measured using the Azocoll assay was significantly elevated by 30 fold in chronic wounds (median 22.8 microg MMP Eq/ml) compared to acute wounds (median 0.76 microg MMP Eq/ml) (p < 0.001). The addition of the matrix metalloproteinase inhibitor Illomostat decreased the matrix metalloproteinase activity by approximately 90% in all samples, confirming that the majority of the activity measured was due to matrix metalloproteinases. Gelatin zymograms indicated predominantly elevated matrix metalloproteinase-9 with smaller elevations of matrix metalloproteinase-2. In addition tissue inhibitor of metalloproteinase-1 levels were analyzed in a small subset of acute and chronic wounds. When tissue inhibitor of metalloproteinase-1 levels were compared to protease levels there was an inverse correlation (p = 0.02, r = - 0.78). In vitro degradation of epidermal growth factor was measured by addition of 125I labelled epidermal growth factor to acute and chronic wound fluid samples. There was significantly higher degradation of epidermal growth factor in chronic wound fluid samples (mean 28.1%) compared to acute samples (mean 0.6%). This also correlated to the epidermal growth factor activity of these wound fluid samples (p < 0. 001, r = 0.64). Additionally, the levels of proteases were assayed in wound fluid collected from 15 venous leg ulcers during a nonhealing and healing phase using a unique model of chronic wound healing in humans. Patients with nonhealing venous leg ulcers were admitted to the hospital for bed rest and wound fluid samples were collected on admission (nonhealing phase) and after 2 weeks (healing phase) when the ulcers had begun to heal as evidenced by a reduction in size (median 12%). These data showed that the elevated levels of matrix metalloproteinase activity decreased significantly as healing occurs in chronic leg ulcers (p < 0.01). This parallels the processes observed in normally healing acute wounds. This data also supports the case for the addition of protease inhibitors in chronic wounds in conjunction with any treatments using growth factors.

Acute Disease↗