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Biomedical subjects

A V Foster

Publications and source records attributed to A V Foster.

15 recordsLinked to original sources
PubMed2001

Bisphosphonates in the treatment of Charcot neuroarthropathy: a double-blind randomised controlled trial.

AIMS/HYPOTHESIS: The management of charcot neuroarthropathy, a severe disabling condition in diabetic patients with peripheral neuropathy, is currently inadequate with no specific pharmacological treatment available. We undertook a double-blind randomised controlled trial to study the effect of pamidronate, a bisphosphonate, in the management of acute diabetic Charcot neuroarthropathy. METHODS: Altogether 39 diabetic patients with active Charcot neuroarthropathy from four centres in England were randomised in a double-blind placebo-controlled trial. Patients received a single infusion of 90 mg of pamidronate or placebo (saline). Foot temperatures, symptoms and markers of bone turnover (bone specific alkaline phosphatase and deoxypyridinoline crosslinks) were measured over the 12 months, in 10 visits. All patients also had standard treatment of the Charcot foot. RESULTS: Mean age of the study group (59 % Type II (non-insulin-dependent) diabetes mellitus) was 56.3 +/- 10.2 years. The mean temperature difference between active and control groups was 3.6 +/- 1.7 degrees C and 3.3 +/- 1.4 degrees C, respectively. There was a fall in temperature of the affected foot in both groups after 2 weeks with a further reduction in temperature in the active group at 4 weeks (active and placebo vs baseline; p = 0.001; p = 0.01, respectively), but no difference was seen between groups. An improvement in symptoms was seen in the active group compared with the placebo group (p < 0.001). Reduction in bone turnover (means +/- SEM) was greater in the active than in the control group. Urinary deoxypyridinoline in the pamidronate treated group fell to 4.4 +/- 0.4 nmol/mmol creatinine at 4 weeks compared with 7.1 +/- 1.0 in the placebo group (p = 0.01) and bone-specific alkaline phosphatase fell to 14.1 +/- 1.2 u/l compared with 18.6 +/- 1.6 u/l after 4 weeks, respectively (p = 0.03). CONCLUSION/INTERPRETATION: The bisphosphonate, pamidronate, given as a single dose leads to a reduction in bone turnover, symptoms and disease activity in diabetic patients with active Charcot neuroarthropathy.

Adult↗
PubMed2000

Infection of foot ulcers with Staphylococcus aureus associated with increased mortality in diabetic patients.

Diabetic patients with foot ulceration have a poorer prognosis than those without ulceration. The reason for this is unclear, but there is considerable interest in the putative links between infection and atherogenesis, and it is notable that diabetic foot ulcers (DFU) are often infected with Staphylococcus aureus and the main cause of death in DFU patients is ischaemic heart disease. We examined the 5 year survival of 71 diabetic patients who presented with foot ulcers that were newly infected (Sa group, n = 56) or not infected at all during the study period (non-Sa group, n = 15) with S. aureus. Twenty-nine patients (52%) infected with S. aureus died compared with three patients (20%) whose foot ulcers were not infected with S. aureus. The patients in the two groups were similar in age and duration of diabetes. The overall five year mortality rate was 10.4% per year for those infected, significantly higher than the average of 4.0% for patients without infection (p = 0.015). None of the patients was bacteraemic or died directly from sepsis. Infection of DFU by S. aureus may increase the risk of death in diabetic patients.

Aged↗
PubMed1999

Why do foot ulcers recur in diabetic patients?

AIM: To investigate factors predisposing to recurrent foot ulceration in patients with diabetes mellitus. METHODS: Two groups of patients who had attended a specialist Diabetes Foot Centre were assessed: relapsers (n = 26), whose foot ulceration had recurred at least twice, and nonrelapsers (n = 25), whose initial ulcer had not recurred for at least 2 years. RESULTS: In the relapser group 10/26 patients waited at least 24 h before reporting symptoms compared with only 2/25 in the nonrelapser group (P < 0.05). Vibration perception threshold (volts) was 38 +/- 12 (mean +/- SD) in relapsers compared with 25 +/- 13 in nonrelapsers (P < 0.005). Cold perception threshold (degrees C) was 9.1 +/- 4.6 in relapsers compared with 5.1 +/- 3.5 in nonrelapsers (P<0.005). HbA1c (%) was significantly raised at 8.5 +/- 1.7 in relapsers compared with 7.6 +/- 1.2 in nonrelapsers (P = 0.03). Alcohol intake was 0.5 (median, interquartile range 0-2) units per day in relapsers compared with 0.0 (median, interquartile range 0-0.25) units in nonrelapsers (P = 0.04). Smoking habits, housing conditions, visual acuity, threshold for warm perception and the Doppler pressure index were not significantly different in the two groups. CONCLUSIONS: Patients who develop recurrent foot ulceration delay in reporting symptoms, when compared with diabetic patients whose foot ulceration does not recur. The relapsers also have evidence of poorer glycaemic control, more neuropathy and increased alcohol intake.

Adult↗
PubMed1997

Randomised placebo-controlled trial of granulocyte-colony stimulating factor in diabetic foot infection.

BACKGROUND: Diabetic foot infections cause substantial morbidity and mortality. Neutrophil superoxide generation, a crucial part of neutrophil bactericidal activity, is impaired in diabetes. Granulocyte-colony stimulating factor (G-CSF) increases the release of neutrophils from the bone marrow and improves neutrophil function. We assessed G-CSF as adjuvant therapy for the treatment of severe foot infections in diabetic patients. METHODS: 40 diabetic patients with foot infections were enrolled in a double-blind placebo-controlled study. On admission, patients were randomly assigned G-CSF (filgrastim) therapy (n = 20) or placebo (n = 20) for 7 days. Both groups received similar antibiotic and insulin treatment. Neutrophils from the peripheral blood of these participants and from healthy controls were stimulated with opsonised zymosan, and superoxide production was measured by a spectrophotometric assay (reduction of ferricytochrome C). FINDINGS: G-CSF therapy was associated with earlier eradication of pathogens from the infected ulcer (median 4 [range 2-10] vs 8 [2-79] days in the placebo group; p = 0.02), quicker resolution of cellulitis (7 [5-20] vs 12 [5-93] days; p = 0.03), shorter hospital stay (10 [7-31] vs 17.5 [9-100] days; p = 0.02), and a shorter duration of intravenous antibiotic treatment (8.5 [5-30] vs 14.5 [8-63] days; p = 0.02). No G-CSF-treated patient needed surgery, whereas two placebo recipients underwent to amputation and two had extensive debridement under anaesthesia. After 7 days' treatment, neutrophil superoxide production was significantly higher in the G-CSF group than in the placebo group (16.1 [4.2-24.2] vs 7.3 [2.1-11.5] nmol per 10(6) neutrophils in 30 min; p < 0.0001). G-CSF therapy was generally well tolerated. INTERPRETATION: G-CSF treatment was associated with improved clinical outcome of foot infection in diabetic patients. This improvement may be related to an increase in neutrophil superoxide production.

Aged↗
PubMed1997

Measurement of markers of osteoclast and osteoblast activity in patients with acute and chronic diabetic Charcot neuroarthropathy.

Excess osteoclast activity is believed to be responsible for the early bone changes associated with Charcot neuroarthropathy in diabetes mellitus. Markers of osteoclast and osteoblast activity were measured in four groups of patients: 16 with an acute Charcot foot, 16 with a chronic Charcot foot, 10 diabetic controls, and 10 non-diabetic controls. Serum carboxyterminal telopeptide of type 1 collagen (1CTP), a marker of osteoclastic bone resorption, was significantly raised in the dorsal venous arch of the acute Charcot foot, 6.1 +/- 1.5 microg l(-1) (mean +/- SD) compared with the chronic Charcot foot 4.1 +/- 1.4, diabetic controls 3.3 +/- 1.4, and non-diabetic controls 2.8 +/- 1.4, p < 0.0001. This local increase in 1CTP was also reflected systemically in a study subgroup of 6 patients with acute Charcot neuroarthropathy, in whom peripheral antecubital vein 1CTP was 9.2 +/- 2.6 compared with 9.0 +/- 3.1 in the foot. In 6 chronic Charcot neuroarthropathy patients, foot (3.8 +/- 1.3) and systemic (4.0 +/- 1.5) 1CTP values were similar. Serum procollagen carboxyterminal propeptide (P1CP), an indicator of osteoblastic bone formation, was not significantly different between the feet of patients with acute Charcot neuroarthropathy 112 +/- 1.5 microg l(-1), patients with chronic Charcot neuroarthropathy 109 +/- 1.5 microg l(-1), diabetic controls 93.5 +/- 2.3 microg l(-1), and non-diabetic controls 90.1 +/- 1.5 microg l(-1). These results suggest that the acute Charcot foot demonstrates excess osteoclastic activity without concomitant increase in osteoblastic function. This may be important in its pathogenesis.

Acute Disease↗
PubMed1995

Reduction of gangrene and amputations in diabetic renal transplant patients: the role of a special foot clinic.

This 4-year prospective study investigated the reasons for high levels of gangrene and major amputation in diabetic renal transplant patients and whether regular multidisciplinary foot care could reduce morbidity. All foot lesions were documented and investigated in 50 diabetic patients, mean age 49.2 +/- 11.0 (SD) years, duration of diabetes 25.3 +/- 9.0 years, time since renal transplantation 60.2 +/- 35.1 months, who attended a special foot clinic monthly for education, vascular and neurological assessment, podiatry and footwear. Foot lesions included: neuropathic ulcers, ischaemic ulcers, traumatic lesions, Charcot's arthropathy, pathological fracture. Treatment included antibiotics, podiatry, footwear, and angioplasty or distal bypass where appropriate. Only 13 patients were deemed ischaemic but peripheral neuropathy was a very common finding (mean VPT 24.8 +/- 12.9 V). Gangrene and major amputations showed a decrease on previous years and healing times for lesions were similar to those previously reported in diabetic patients without renal transplants. The majority of foot lesions, both in soft tissue and bone, were related to neuropathy and trauma and responded well to optimal foot care within the renal unit. Gangrene and major amputations were usually preventable.

Ambulatory Care Facilities↗
PubMed1994

Application of OpSite film: a new and effective treatment of painful diabetic neuropathy.

The aim of the study was to assess the effect of application of OpSite dressings on the pain and quality of life in 33 patients with chronic diabetic neuropathy. The effect of OpSite was compared with no treatment. After a run-in period of 2 weeks, OpSite was applied to one of the painful legs for 4 weeks. This was followed by another period of 4 weeks when OpSite was switched to the opposite leg. Pain was assessed by visual analogue scale and the primary analysis variable was within patient difference in pain between OpSite leg and no treatment leg at week 4 corrected for baseline. Secondary variables were paracetamol pill ingestion and the quality of life dimensions, sleep, mobility, contact discomfort, appetite, and mood. Changes in these variables from baseline to weeks 4 and 8 were analysed. There was a significantly greater reduction in pain in the OpSite treated limbs than the control limbs (p < 0.001). By week 4 paracetamol intake also declined significantly (p = 0.034) and patients experienced a significant improvement in contact discomfort, sleep, mood, appetite, and mobility (p < 0.002 for all 5 variables). OpSite appeared to alleviate the pain associated with diabetic painful neuropathy and thus improved patients' quality of life.

Adult↗
PubMed1993

Abnormal digital pressure measurements in diabetic neuropathic foot ulceration.

The diabetic neuropathic ulcer is typically slow to heal and recurrent. Macrovascular insufficiency is usually excluded as foot pulses are present and ankle:brachial pressure ratios are not decreased. These assessments cannot however exclude more distal vascular disease. Digital pressure measurements enable a reliable assessment of the distal peripheral vascular status to be made. The aim of this study was therefore to use toe pressures to assess the contribution of distal ischaemia in the pathogenesis of the neuropathic ulcer. Sixteen diabetic patients with recurrent neuropathic foot ulceration had their toe pressures compared to 10 neuropathic patients without a history of foot ulceration, 10 diabetic control subjects, and 11 normal subjects. Four non-diabetic patients with neuropathy and foot ulceration were also assessed. All subjects had ankle:brachial pressure indices > or = 1. Toe pressure was assessed using laser Doppler flowmetry to record the return of skin blood flow. The toe:brachial pressure index (TBI) was then calculated. The diabetic patients with a history of recurrent neuropathic ulceration, had the lowest mean TBI, 0.63 +/- 0.14 (SD), compared to the non-ulcerated diabetic neuropathy patients, the diabetic control subjects, and the normal subjects. 0.84 +/- 0.11, 0.82 +/- 0.1, and 0.81 +/- 0.07, p < 0.01, respectively. Three of the four non-diabetic patients with neuropathic foot ulceration also had an abnormally low TBI. Reduced toe pressure measurements are thus found to be associated with neuropathic foot ulceration. The contribution of distal ischaemia in the pathogenesis of the diabetic neuropathic foot ulcer needs to be evaluated.

Adult↗
PubMed1992

Selective neuropathy and preserved vascular responses in the diabetic Charcot foot.

Charcot arthropathy is a disabling complication of diabetic neuropathy. It is however, unclear why it occurs in only a small number of neuropathic patients. We have studied 12 diabetic patients (10 insulin-dependent) with an acute Charcot arthropathy, and compared their neuropathy and vascular responsiveness with 12 diabetic patients (10 insulin-dependent) with recurrent neuropathic foot ulceration, 12 diabetic control subjects (9 insulin-dependent) and 10 normal non-diabetic subjects. The Charcot arthropathy patients demonstrated a preservation of warm perception, 6 (5.5) degrees C, but complete loss of peripheral cold perception, 10 (0) degrees C, p less than 0.001 (median (interquartile range)). This contrasted with the ulcerated neuropathy patients, who had equally severe impairement of both warm and cold sensory thresholds, 10(0.5) degrees C vs 10(1) degrees C, respectively, the diabetic control subjects who were able to detect a 2 (1.3) degrees C warm stimulus and 3 (3.5) degrees C cold stimulus and the normal subjects, whose warm threshold was 2 (1) degrees C and cold was 2 (1) degrees C. Light touch perception at the foot was preserved in the Charcot patients 4 (4) g vs 100 (50) g, p less than 0.0002, in the ulcerated neuropathy patients. Vibration perception at the great toe and cardiovascular autonomic function tests (heart rate variability, Valsalva ratio and postural systolic blood pressure fall) were abnormal in both the Charcot patients and ulcerated neuropathy group, with no differences seen between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Arthropathy, Neurogenic↗
PubMed1986

Clonal analysis of expression of epithelial antigens in cultures of normal human breast.

Cells from normal human breast epithelium were cloned in monolayer culture and the clones were stained with monoclonal antibodies. Tissue was from reduction mammoplasty operations. Cloning efficiencies were 5-30%. Two types of clone were identified: 10 to 30% were of relatively spread cells whose boundaries were often difficult to see by phase-contrast microscopy but where they were visible they appeared as dark lines. The edges of the clones usually appeared to be under tension. These clones were stained by two monoclonal antibodies, LICR-LON-M8 and M24, that stain luminal epithelial cells in the intact tissue, but not myoepithelial or stromal cells. Within a clone the cells showed a full range of antigenic phenotypes. This was confirmed for clones grown from single cells that had been isolated manually. The second type of clone was more compact with little evidence of tension at the edges, and cell boundaries were clearly visible and bright under phase contrast. These clones were not stained by antibodies M8 or M24. Both types of clone stained with a third monoclonal antibody that is specific for luminal epithelial cells in the intact tissue, LICR-LON-M18, but the distribution of staining was different in the different types of clone. The simplest interpretation of the two types of clone is that luminal epithelial cells give rise to the spread type of clone while the myoepithelial cells give rise to the more abundant and vigorous compact clones. Alternatively, the compact clones may be from luminal epithelial cells that have lost differentiated characteristics.

Antibodies, Monoclonal↗
PubMedDate not supplied

Paradoxical blood flow responses in the diabetic neuropathic foot: an assessment of the contribution of vascular denervation and microangiopathy.

Blood flow is abnormal in the diabetic neuropathic foot, and this may be of importance in the pathogenesis of complications. Arteriovenous shunting is increased, and blood flow through these channels may paradoxically decrease in response to local heating. Peak skin blood flow is also reduced in these patients. It is not known whether these blood flow abnormalities may reflect diabetic microangiopathy, or whether they simply reflect vascular denervation. The skin blood flow response to a local thermal stimulus was studied in four non-diabetic patients with a unilateral traumatic neuropathy and foot ulceration. All showed a decrease in skin blood flow (to 68% of basal) at the great toe during local heating in the neuropathic limb, in contrast to the normal limb, in which blood flow increased to 180% of basal. Peak skin blood flow was also greatly reduced in the neuropathic limb, being only 29% of the normal limb. Neuropathy alone can be responsible for abnormal skin blood flow responses in the neuropathic foot.

Adolescent↗