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W Jeffcoate

Publications and source records attributed to W Jeffcoate.

At least 19 recordsLinked to original sources

Does close glycaemic control promote healing in diabetic foot ulcers? Report of a feasibility study.

AIM: To undertake a pilot study to determine the feasibility of a definitive trial of the effect of close glycaemic control on healing of foot ulcers in diabetes. METHODS: All patients attending a dedicated multidisciplinary clinic for the management of established ulcers over a 20-week period were systematically screened for inclusion in a randomised, single-blinded study. FINDINGS: Two hundred individuals with foot ulcers attended the clinic during the recruitment period, but only nine met the predefined inclusion and exclusion criteria. One of these was withdrawn because of an adverse event immediately before recruitment, two proved incapable of administering insulin injections and were withdrawn prior to randomization. Four withheld consent, and one was advised to withhold consent by his community nurse. One was randomised and completed the 3-month study. The study was abandoned at 20 weeks when it was decided that it would be unlikely that a sufficient number of suitable patients would ever be recruited, and that it would therefore be unethical to approach further subjects. CONCLUSIONS: It was concluded that although evidence is required to guide future practice in this field, the study design chosen was not feasible.

Adolescent↗

Ulcer-free survival following management of foot ulcers in diabetes.

AIMS: Measures of healing rate may not give a complete indication of the effectiveness of overall management of diabetic foot ulcers. Apart from healing and speed of healing, the outcomes of greatest importance to the patient are avoidance of any amputation and remaining free from any recurrence. We have documented the number of patients presenting with diabetic foot ulcers who become ulcer free and examined the value of documenting ulcer-free survival. METHODS: All referrals to a specialist diabetic foot clinic over a 31-month period were analysed and outcomes were determined after a minimum follow-up of 6 months. RESULTS: Three hundred and seventy patients were referred with a total of 1031 ulcers. One hundred and twenty-one (32.7%) never became ulcer free: 56 (46.3% of 121) remained unhealed, the ulcers of 12 (9.9% of 121) had been resolved by amputation, two remained unhealed after amputation (1.7% of 121) and 51 (13.8% of 370) had died. Two hundred and thirty-one (62.4% of 370) became ulcer free at some stage. Five of these were excluded because of an earlier amputation. Ninety-one of the remaining 226 (40.3%) developed a recurrent or new ulcer after a median 126 days. Of the 135 who did not have a recurrence, 133 (58.8% of 226; 35.9% of 370) survived ulcer free and with limbs intact, while two died. Outcome was unknown in 18 (4.9%). Those who never became ulcer free were older (P < 0.001) and with a greater prevalence of ischaemia (P < 0.001). Those who healed but went on to suffer a new ulcer had a greater prevalence of neuropathy (P = 0.027) than those who remained ulcer free. CONCLUSIONS: The use of ulcer-free survival can be used as an indication of the effectiveness of foot ulcer management. It could be adopted as a measure to compare performance between different specialist units.

Age Factors↗

Vascular calcification and osteolysis in diabetic neuropathy-is RANK-L the missing link?

Diabetic neuropathy is associated with osteopenia and calcification of vascular smooth muscle cells. These changes are most marked in patients with acute neuropathic osteoarthropathy (Charcot foot), in which osteopenia is universal and the prevalence of vascular calcification exceeds 90%. While it has been thought that both osteopenia and vascular calcification may be linked to sympathetic denervation with increased peripheral limb perfusion, the cellular mechanism was not clear. However, the recent recognition that the receptor activator of nuclear factor kappa B ligand (RANK-L)/osteoprotegerin (OPG) signalling pathway is central to the processes regulating bone turnover in a wide variety of medical conditions has raised the possibility that the same cytokines may be involved in the osteolysis which accompanies diabetic neuropathy. This is made more likely by the realisation that the RANK-L/OPG pathway is also thought to mediate the calcification of vascular smooth muscle cells in coronary and peripheral vascular disease. The circumstantial evidence underpinning this hypothesis is reviewed here, and it is suggested that the unregulated activation of RANK-L-mediated effects on bone and arteries may be triggered by the loss of nerve-derived peptides, e.g. calcitonin gene-related peptide, which normally exert a moderating influence on the pathway.

Calcitonin Gene-Related Peptide↗

Mortality in patients with diabetic neuropathic osteoarthropathy (Charcot foot).

OBJECTIVE: To determine the mortality of a population of patients diagnosed with Charcot neuropathic osteoarthropathy managed by a single specialist unit and to compare the results with a control population. METHODS: We have undertaken a retrospective analysis of all cases of Charcot foot on the comprehensive database which has been maintained at the specialist diabetic foot clinic at the City Hospital, Nottingham since 1982. Survival and the incidence of amputation (major and minor) was compared with a control population referred with uncomplicated neuropathic ulceration. Controls were individually matched for gender, age (+/-2 years), disease type, disease duration (+/-2 years) and year of referral (+/-3 years). RESULTS: Forty-seven cases (21 female, 26 male) of Charcot foot were identified, of whom 18 (38.3%) had Type 1 diabetes. Mean age and disease duration at presentation were 59.2 +/- 13.4 (sd) and 16.2 +/- 11.2 years, compared with 59.7 +/- 12.6 and 16.3 +/- 11.2 years, respectively, in the controls. Twenty-one (44.7%) of those with Charcot had died, after a mean interval of 3.7 +/- 2.8 years. This compared with 16 (34.0%) after a mean 3.1 +/- 2.7 years in the control group. Mean duration of follow-up in the survivors was 4.7 +/- 4.9 years (Charcot) and 5.3 +/- 3.9 years (controls). A total of 11 (23.4%) Charcot patients had had a major amputation on the side of the index lesion, compared with five (10.6%) controls. There was no difference between the two groups (P > 0.05, Chi-square). CONCLUSIONS: The mortality in this group of patients with Charcot foot was higher than expected. Nevertheless, there was no difference between those with Charcot and those with uncomplicated neuropathic ulceration. It is possible that it is neuropathy, rather than Charcot osteoarthropathy, which is independently associated with increased mortality in diabetes. The mechanism underlying any such association is not known. There is a need for a formal, prospective, multicentre study to investigate the life expectancy and cardiovascular risk of those with Charcot osteoarthropathy.

Adult↗

Why did the 5th Earl of Derby die?

The unexpected death of Ferdinando Stanley, 5th Earl of Derby, on April 16, 1594 was an event of major political importance in the later years of Queen Elizabeth I of England. When he had succeeded his father at the age of 38 he became head of one of the most influential families in the country. He also had a claim to the throne if Elizabeth died without naming a successor. Yet within seven months of entering into his inheritance, this previously fit man was suddenly taken ill and died a fortnight later. His death was so significant that the historian John Stow recorded his illness in great detail (Fig. 1).(1) Stow's remarkable account is compatible with a sinister interpretation of the cause.

Acute Kidney Injury↗

The Charcot foot.

AIMS: To review the clinical manifestations of the Charcot foot in diabetes mellitus, with particular reference to theories concerning aetiology. METHODS: Systematic review of the published literature, searching for the keywords 'Charcot', 'foot and diabetes' and 'neuropathy' on Medline, as well as by examination of the references in recent published reviews. CONCLUSIONS: The Charcot foot of diabetes mellitus is a common problem, and yet is not widely recognized by non-specialists. The failure of professionals to identify the condition in its early phases is probably largely responsible for the gross deformity which follows continued weight-bearing. The condition is confined to those with severe peripheral neuropathy. It is thought to result from three factors: motor neuropathy leading to the development of abnormal forces within the foot, subsequent disorganization of the foot as a result of associated osteopenia and progressive destruction from continued weight-bearing, enabled by reduced pain sensation. The cause of the osteopenia is not known, but it is associated with increased bone blood flow, which may be mainly the result of loss of sympathetic innervation. The importance of increased limb blood flow in the pathogenesis of the Charcot foot has been recognized for over a century. Paradoxically, the increased flow is associated with evidence of macrovascular disease, in that the prevalence of vascular calcification of pedal vessels approaches 90%. After an interval of many months, the condition tends to evolve: the increased blood flow lessens, the osteopenia is reduced and the disorganized bones become sclerotic. This tendency for the condition to evolve remains unexplained, since it would not be expected if the condition was caused solely by progressive denervation. As a result, it is suggested that another factor may be involved in the pathogenesis of the Charcot foot: an abnormal vasomotor reflex, analogous to reflex sympathetic dystrophy, occurring against a background of severe peripheral neuropathy. The resolution of the condition occurs because it is the reflex component of the hyperaemia which proves self-limiting.

Diabetic Foot↗

Assessment of corticosteroid replacement therapy in adults with adrenal insufficiency.

Recent work has taught us that our conventional approach to corticosteroid replacement therapy requires review. Specifically, the doses of hydrocortisone we have used are probably too high for the majority, and should ideally be administered in three or more doses through the day. Nevertheless, there is not much hard evidence that excessive glucocorticoid replacement per se will lead to adverse effects such as osteoporosis, even though it may exacerbate any tendency in those who are predisposed to it for other reasons. As such, there is no compelling need for using determinations of either UFC excretion or of the serum cortisol profile in the routine management of patients on replacement therapy. Nevertheless, such measures may be considered in those thought to be at particular risk of osteoporosis, and in whom it is felt that special effort should be made to ensure that they are receiving the minimum dose possible. In such circumstances, a cortisol day curve is likely to be of more value than measurement of UFC.

17-alpha-Hydroxyprogesterone↗

Making sense.

Explore the source record for details and available documents.

Communication↗

Endocrine investigation of gonadal dysfunction.

This article reviews the hormone assays available for the assessment of gonadal function and some pitfalls in their interpretation. Simple strategies are suggested for the investigation of disorders of gonadal function in males and females. Emphasis is placed on relating the indications for hormone assays to the appropriate clinical context.

Endocrine System Diseases↗