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Biomedical subjects

E B Jude

Publications and source records attributed to E B Jude.

At least 19 recordsLinked to original sources
PubMed2006

Simultaneous pulmonary and cerebral oedema, and multiple CNS infarctions as complications of diabetic ketoacidosis: a case report.

We present a case of a 29-year-old woman with known Type 1 diabetes who presented with diabetic ketoacidosis (DKA). Despite appropriate treatment and initial improvement, 12 h after initiation of treatment she deteriorated rapidly and developed pulmonary oedema, cerebral oedema and multiple infarctions of the brain and cervical spinal cord. This resulted in spastic quadraparesis and she has remained wheelchair-bound. These complications of DKA are rare and unpredictable. In this case report we discuss the proposed aetiologies of these complications with reference to our case report and highlight the importance of vigilance for early signs of these complications during the treatment of all patients with DKA.

Adult↗
PubMed2003

Methicillin-resistant Staphylococcus aureus in the diabetic foot clinic: a worsening problem.

AIMS: To determine if there has been a change in the prevalence of pathogenic organisms in foot ulcers in diabetic patients in 2001 compared with our previous study in 1998. METHODS: A retrospective analysis of wound swabs taken from infected foot ulcers in diabetic patients attending the outpatient clinic in the Manchester Foot Hospital over a twelve-month period. A total of 63 patients with positive wound swabs were identified. RESULTS: Gram-positive aerobic bacteria still predominate (84.2%) and the commonest single isolate remains Staphylococcus aureus (79.0%) which is higher than we previously reported. MRSA was isolated in 30.2% of the patients which is almost double the proportion of MRSA-affected patients three years ago. This did not appear to be related to prior antibiotic usage. There was no increase in hospitalisation because of MRSA infection. CONCLUSIONS: The problem of MRSA continues to increase despite the precautions taken to prevent MRSA spread. There is a need for a multi-centre study looking into the prevalence of MRSA in diabetic foot ulcer and how this can be reduced in the diabetic foot clinic.

Diabetic Foot↗
PubMed2002

Transforming growth factor-beta 1, 2, 3 and receptor type I and II in diabetic foot ulcers.

AIMS: To study the distribution of transforming growth factor-beta (TGF-beta) 1, 2 and 3, and TGF-beta receptor types I and II in diabetic foot ulcers, diabetic skin and normal skin by immunohistochemistry, immunofluorescence and Western blotting. We also compared the TGF-betas with those of chronic venous ulcers. METHODS: Skin biopsies were obtained from the leg or the foot of non-diabetic and diabetic subjects, and from the edge of diabetic foot ulcers and chronic venous ulcers. Distribution (by immunofluorescence and immunocytochemistry) of TGF-beta 1, 2 and 3 and TGF-beta receptors (RI and RII) was done by staining 8-microm skin sections using appropriate antibodies. Protein levels of TGF-beta were measured by Western blot analysis. RESULTS: TGF-beta3 expression was increased in the epithelium at the edge of diabetic foot ulcers, being more intense than diabetic and normal skin (P = 0.03, 0.02, respectively), as was its expression in venous ulcers compared with normal skin. However, TGF-beta1 expression was not increased in diabetic foot ulcers and chronic venous ulcers, and was comparable to diabetic and normal skin. There was also no increase for the receptors in diabetic foot ulcers. CONCLUSION: The lack of TGF-beta1 up-regulation in both diabetic foot ulcers and venous ulcers may explain the impaired healing in these chronic wounds, and could represent a general pattern for chronicity.

Activin Receptors, Type I↗
PubMed2002

The relationship between blood glucose excursions and painful diabetic peripheral neuropathy: a pilot study.

AIMS: Peripheral neuropathy affects 30% of Type 1 diabetic patients. Unfortunately, 10-20% of affected patients have disabling symptoms. The aim of this study was to examine the relationship between blood glucose excursions and pain in patients with symptomatic diabetic neuropathy. METHODS: Twenty Type 1 diabetic patients with peripheral neuropathy (10 painful and 10 painless) wore a continuous glucose monitoring system for 3 days. Symptomatic patients kept a daily pain score diary. The mean amplitude of glycaemic excursions (MAGE) and the M-values (measure of glucose deviations from an arbitrarily selected point) were calculated. RESULTS: Groups were matched for (mean +/- sd) age: 52.0 +/- 11.1 years; duration of diabetes: 24.8 +/- 10.7 years; HbA1c: 9.7 +/- 2.3%; duration of neuropathy: 5.6 +/- 2.6 years; and CGMS performance. The painful group had a greater mean glucose (12.1 +/- 2.9 mmol/l vs. 9.3 +/- 1.9 mmol/l, P = 0.02), a greater M-value (68.4 vs. 31.1, P = 0.02) and more glycaemic excursions (13 vs. 10, P < 0.01), compared with the painless group. However, there was no difference in the MAGE between both groups, and no correlation between the number of glycaemic excursions and the number of painful episodes in the painful group. CONCLUSIONS: Patients with painful neuropathy have greater glucose flux and possibly poorer diabetes control, compared with patients with painless neuropathy.

Adult↗
PubMed2002

Natural history and prognostic factors of diabetic nephropathy in type 2 diabetes.

BACKGROUND: The causes and mechanisms of increased mortality of patients with diabetic nephropathy are unclear, and its natural history is poorly understood. AIM: To evaluate risk factors for mortality in type 2 diabetic patients with nephropathy. DESIGN: Retrospective study of clinical and biochemical parameters in diabetic nephropathic patients and controls sampled from a secondary care register. METHODS: We studied 170 type 2 diabetic patients (from 1987 to 1995) with nephropathy (proteinuria >0.5 g/24 h) and 170 non-nephropathic patients. Follow-up was until death or December 1997. Details of demographics, clinical and treatment history were obtained from medical records. RESULTS: Mean follow-up was 5.3 years. Of the patients with nephropathy at baseline, 63 (37%) died compared with 14 (8%) non-nephropathic patients (chi(2)=53.8, p<0.0001). Age- and sex-adjusted all-cause mortality rates were 8.1 (6.4, 9.8) and 1.4 (0.5, 2.2) deaths per 100 person-years, respectively (rate ratio 5.8). Forty-four patients (57%) died from cardiovascular causes (rate ratio 5.4). Mortality was directly proportional to degree of proteinuria: 0.5-2 g/24 h, 4.6 (2.9-7.1); >2 g/24 h, 9.9 (7.3-13.5) per 100 patient-years. A 36% (5-78%) excess risk of mortality was observed for each log unit increase in proteinuria. Multivariate Cox regression analyses confirmed a five-fold excess risk for all-cause and cardiovascular mortality in patients with nephropathy compared with those without. This was independent of other risk factors including baseline age [5% (1-8%)/year], creatinine [2.5 (1.12-5.6)/10 micromol/l] and glycaemic control (HbA(1c)) [15% (1-31%) per 1% rise]. CONCLUSIONS: Proteinuria is a potentially preventable and reversible risk factor associated with high mortality in type 2 diabetic patients. Prevention of the development of overt nephropathy and improvement in diabetes control may reduce mortality in these patients.

Aged↗
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↗
PubMed2001

Update on Charcot neuroarthropathy.

Charcot neuroarthropathy is not uncommon in diabetic patients with peripheral neuropathy. Often, the condition is misdiagnosed for cellulitis or osteomyelitis and treatment is delayed. A high index of suspicion is required in these patients to initiate appropriate treatment early. This article covers the pathogeneses of this condition and briefly describes the recent studies performed to understand the underlying etiopathogenetic factors of this devastating condition. Lastly, it mentions the recently completed multicenter trial using bisphosphonates in diabetic Charcot neuroarthropathy.

Arthropathy, Neurogenic↗
PubMed2001

The effects of ulcer size and site, patient's age, sex and type and duration of diabetes on the outcome of diabetic foot ulcers.

AIMS: The outcome of foot ulcers is affected by wound depth, infection, ischaemia and glycaemic control. The aim of this study was to determine the effects of ulcer size, site, patient's age, sex and type and duration of diabetes on the outcome of diabetic foot ulcers. METHODS: Diabetic patients with new foot ulcers presenting during a 12-month period had demographics and ulcer characteristics recorded at presentation. Ulcers were followed-up until an outcome was noted. RESULTS: One hundred and ninety-four patients (77% males) with a mean (+/- SD) age and duration of diabetes of 56.6 +/- 12.6 and 15.4 +/- 9.9 years, respectively, were included in the study. The majority of ulcers were neuropathic (67.0%) and present on the forefoot (77.8%) with a median (interquartile range) area of 1.5 (0.6-4.0) cm2. Amputations were performed for 15% of ulcers; 65% healed; 16% remained unhealed and 4% of patients died. The median (95% confidence interval) time to healing was 10 (8.8-11.6) weeks. Ulcer area at presentation was greater in the amputation group compared to healed ulcers (3.9 vs. 1.2 cm2, P < 0.0001). Ulcer area correlated with healing time (rs = 0.27, P < 0.0001) and predicted healing (P = 0.04). Patient's age, sex, duration/type of diabetes, and ulcer site had no effect on outcome. CONCLUSIONS: Ulcer area, a measure of ulcer size, predicts the outcome of foot ulcers. Its inclusion into a diabetic wound classification system will make that system a better predictor of outcome.

Age Factors↗
PubMed2001

A role for mitogen-activated protein kinases in the etiology of diabetic neuropathy.

The onset of diabetic neuropathy, a complication of diabetes mellitus, has been linked to poor glycemic control. We tested the hypothesis that the mitogen-activated protein kinases (MAPK) form transducers for the damaging effects of high glucose. In cultures of adult rat sensory neurons, high glucose activated JNK and p38 MAPK but did not result in cell damage. However, oxidative stress activated ERK and p38 MAPKs and resulted in cellular damage. In the dorsal root ganglia of streptozotocin-induced diabetic rats (a model of type I diabetes), ERK and p38 were activated at 8 wk duration, followed by activation of JNK at 12 wk duration. We report activation of JNK and increases in total levels of p38 and JNK in sural nerve of type I and II diabetic patients. These data implicate MAPKs in the etiology of diabetic neuropathy both via direct effects of glucose and via glucose-induced oxidative stress.

Animals↗
PubMed2001

A comparison of two diabetic foot ulcer classification systems: the Wagner and the University of Texas wound classification systems.

OBJECTIVE: In this study the following two ulcer classification systems were applied to new foot ulcers to compare them as predictors of outcome: the Wagner (grade) and the University of Texas (LT) (grade and stage) wound classification systems. RESEARCH DESIGN AND METHODS: Ulcer size, appearance, clinical evidence of infection, ischemia, and neuropathy at presentation were recorded, and patients were followed up until healing or for 6 months. RESULTS: Of 194 patients with new foot ulcers, 67.0% were neuropathic, 26.3% were neuroischemic, 1.0% were ischemic, and 5.7% had no identified underlying factors. Median (interquartile range [IQR]) ulcer size at presentation was 1.5 cm2 (0.6-4.0). Lower-limb amputations were performed for 15% of ulcers, whereas 65% healed [median (IQR) healing time 5 (3-10) weeks] and 16% were not healed at study termination; 4% of patients died. Wagner grade (P < 0.0001), and UT grade (P < 0.0001) and stage (P < 0.001) showed positive trends with increased number of amputations. For UT stage, the risk of amputation increased with infection both alone (odds ratio [OR] = 11.1, P < 0.0001) and in combination with ischemia (OR = 14.7, P < 0.0001), but not significantly with ischemia alone (OR = 4.6, P = 0.09). Healing times were not significantly different for each grade of the Wagner (P = 0.1) or the UT system (P = 0.07), but there was a significant stepwise increase in healing time with each stage of the UT system (P < 0.05), and stage predicted healing (P < 0.05). CONCLUSIONS: Increasing stage, regardless of grade, is associated with increased risk of amputation and prolonged ulcer healing time. The UT system's inclusion of stage makes it a better predictor of outcome.

Adult↗
PubMed2001

Peripheral arterial disease in diabetic and nondiabetic patients: a comparison of severity and outcome.

OBJECTIVE: The aim of this study was to quantify the distribution of peripheral arterial disease in the diabetic and nondiabetic population attending for angiography and to compare severity and outcome between both groups of patients. RESEARCH DESIGN AND METHODS: Randomly selected lower-extremity angiograms were examined according to the Bollinger system. Patient demographics and medical history were recorded and case notes were examined to determine which patients later underwent a revascularization procedure or amputation and which patients had died. RESULTS: A total of 136 arteriograms obtained between 1992 and 1996 were analyzed. The age (mean +/- SD) of the patients was 64.7 +/- 10.8 years. Diabetic patients (43%) and nondiabetic patients were of similar age (63.9 +/- 10.4 vs. 65.3 +/- 11.1 years, P = 0.43), with a similar history of smoking (81.0 vs. 76.9%, P = 0.26), ischemic heart disease (41.4 vs. 37.2%, P = 0.54), and hypercholesterolemia (24.4 vs. 30.8%, P = 0.48). However, there were a greater proportion of hypertensive patients in the diabetic group (63.8 vs. 39.7%, P = 0.006). Diabetic patients had greater severity of arterial disease in the profunda femoris and all arterial segments below the knee (P = 0.02). A greater number of amputations occurred in the diabetic group: diabetic patients were five times more likely to have an amputation (41.4 vs. 11.5%, odds ratio [OR] 5.4, P < 0.0001). Mortality was higher in the diabetic group (51.7 vs. 25.6%, OR 3.1, P = 0.002), and diabetic patients who died were younger at presentation than nondiabetic patients (64.7 +/- 11.4 vs. 71.1 +/- 8.7 years, P = 0.04). CONCLUSIONS: In patients with peripheral arterial disease, diabetic patients have worse arterial disease and a poorer outcome than nondiabetic patients.

Aged↗
PubMed2000

Lack of insulin-like growth factor 1 (IGF1) in the basal keratinocyte layer of diabetic skin and diabetic foot ulcers.

Wound healing, including re-epithelialization, is delayed in diabetes. Growth factors influence the healing process and amongst these, insulin-like growth factor (IGF) has been shown to stimulate keratinocyte proliferation in vitro. Monoclonal antibodies to insulin-like growth factors 1 and 2 (IGF1 and IGF2) were used to investigate their distribution in diabetic foot ulcers and surrounding tissues by immunohistochemistry, compared with diabetic and non-diabetic uninjured skin. IGF2 was found throughout the epidermis (stratum granulosum, spinosum, and basale) in all three groups. Staining for IGF2 was intense in both normal and diabetic skin as well as in diabetic foot ulcers, being greatest at the ulcer edge. IGF1, in comparison, was found throughout the epidermis of non-diabetic skin; expression was restricted to the stratum granulosum and spinosum of uninjured diabetic skin and was absent in the basal layer at the ulcer edge. A similar absence of IGF1 in dermal fibroblasts was found in tissue sections from diabetic patients. This lack of expression of IGF1 within the basal layer and fibroblasts may contribute to retarded wound healing in diabetes mellitus.

Aged↗
PubMed2000

Expression of nitric oxide synthase isoforms and arginase in normal human skin and chronic venous leg ulcers.

Chronic venous ulcers, an example of abnormal wound healing, show chronic inflammation with defective matrix deposition which together with the underlying vascular pathology, result in delayed healing. L-arginine is known to be metabolized by one of two pathways: nitric oxide synthase (NOS), producing nitric oxide (NO), or arginase, producing ornithine. NO is involved in many pathological conditions including vascular and inflammatory disorders. This study therefore investigated the distribution, level and activity of NOS and arginase in chronic venous ulcers in comparison with normal skin, using immunocytochemistry, western blotting, and enzyme assays. The results demonstrated an increased distribution of both NOS and arginase in chronic venous ulcer tissue compared with normal skin, with inflammatory cells and vascular endothelial cells as the main sources. These data were confirmed by western blot analysis, which showed increased levels of both enzymes in chronic venous ulcers. Moreover, there was significantly increased activity of both total NOS (p<0.04) and inducible NOS (p<0.05) in chronic venous ulcer tissue compared with normal skin, and significantly increased activity of arginase (p<0.01) in chronic venous ulcer tissue in comparison with normal skin. NO is known to combine with hydroxyl free radicals forming peroxynitrite, a potent free radical which causes tissue destruction. NO overexpression in chronic venous ulcers may be involved directly or indirectly (through production of peroxynitrite) in the pathogenesis and delayed healing of chronic venous ulcers, through its effects on vasculature, inflammation, and collagen deposition. Arginase is known to enhance matrix deposition. Thus, increased levels of arginase in chronic venous ulcers could contribute to the pathogenesis of lipodermatosclerosis associated with chronic venous insufficiency, predisposing to the formation of chronic venous ulcers and also to matrix cuff formation around blood vessels.

Arginase↗
PubMed2000

Prolonged hypoglycaemia following surgical removal of phaeochromocytoma.

We report a 34-year-old woman with secondary hypertension diagnosed with a left-sided phaeochromocytoma. Excision of the tumour resulted in recurrent hypoglycaemia up to 6 days post-operatively. We discuss the pathogenesis of hypoglycaemia following removal of the tumour and put forward hypothesis for the recurrent hypoglycaemia.

Adrenal Gland Neoplasms↗
PubMed1999

The role of nitric oxide synthase isoforms and arginase in the pathogenesis of diabetic foot ulcers: possible modulatory effects by transforming growth factor beta 1.

AIMS/HYPOTHESIS: L-arginine, an amino acid involved in wound healing, is metabolised by one of two pathways; nitric oxide synthase and arginase. If metabolised by nitric oxide synthase, this can result in tissue destruction, or matrix deposition if metabolised by arginase. The aim therefore was to investigate the role of these enzymes in the pathogenesis of diabetic foot ulcers. METHODS: The activity, proteins by Western blot analysis and cellular distribution (using immunocytochemistry) of these enzymes were measured in diabetic foot ulcers, diabetic skin and normal skin. RESULTS: Total and inducible nitric oxide synthase (p < 0.001) and endothelial nitric oxide synthase were increased in diabetic ulcers compared with diabetic and normal skin and were associated with increased plasma nitrite concentrations in diabetic ulcers (p < 0.05). Inducible nitric oxide synthase was the major isoform, with the macrophage being the predominant cellular source. Similarly arginase activity was increased (p < 0.01) in diabetic ulcers. The protein levels corroborated with the activity data, with the fibroblast being the major cellular source. The spatial and cellular distribution of the two enzyme systems was distinct. Transforming growth factor-beta1 was decreased in diabetic ulcers in comparison with diabetic skin and normal skin. CONCLUSION/INTERPRETATION: Increased nitric oxide synthase activity in diabetic foot ulcers may be responsible for the impaired healing in this disease. Furthermore, the increased activity of arginase could account for the characteristic callus formation around these ulcers. In addition, the lower concentrations of transforming growth factor-betal in diabetic ulcers may explain the raised concentrations of nitric oxide in this condition.

Arginase↗
PubMed1999

Methicillin-resistant Staphylococcus aureus: an increasing problem in a diabetic foot clinic.

AIM: To study the prevalence of pathogenic organisms and the prevalence and outcome of methicillin-resistant Staphylococcus aureus (MRSA) infection in foot ulcers in diabetic patients. METHODS: A retrospective analysis of wound swabs taken from infected foot ulcers in diabetic patients, selected from an outpatient diabetic foot clinic. Seventy-five patients (79 ulcers) with positive wound swabs were included. Size of ulcer and time to healing, in particular for MRSA-infected ulcers, were measured in all patients. RESULTS: Gram-positive aerobic bacteria were the commonest micro-organism isolated (56.7%) followed by gram-negative aerobic bacteria and anaerobes (29.8% and 13.5%, respectively). Of the gram-positive aerobes, S. aureus was found most frequently and 40% were MRSA. MRSA was isolated more commonly in patients treated with antibiotics prior to the swab compared to those who had not received antibiotics (P = 0.01). Patients whose foot ulcers were infected by MRSA had longer healing time than patients whose ulcers were infected by methicillin-sensitive S. aureus (mean (range) 35.4 (19-64) and 17.8 (8-24) weeks, respectively, P = 0.03). CONCLUSION: MRSA infection is common in diabetic foot ulcers and is associated with previous antibiotic treatment and prolonged time to healing. Further studies are required to assess the need for antibiotics in treating foot ulcers in diabetes and to assess the optimum therapeutic approach to this problem.

Aged↗