The Ulster medical journal 06/2007; 76(2):117.
ABSTRACT: There have been a few reports on long-term remission rates after apparent early remission following pituitary surgery in the management of Cushing's disease. An undetectable postoperative serum cortisol has been regarded as the result most likely to predict long-term remission. Our objective was to assess the relapse rates in patients who underwent transsphenoidal surgery in order to determine whether undetectable cortisol following surgery was predictive of long-term remission and whether it was possible to have long-term remission when early morning cortisol was measurable but not grossly elevated. Endocrinological factors associated with late relapse were also studied.
We reviewed the long-term outcome in 63 patients who had pituitary surgery for the treatment of Cushing's disease between 1979 and 2000.
Case notes were reviewed and the current clinical and biochemical status assessed. Our usual practice was that early after the operation, an 08:00 h serum cortisol was measured 24 h after the last dose of hydrocortisone. This was followed by a formal low-dose dexamethasone suppression test. Current clinical status and recent 24-h urinary free cortisol values were used as an index of activity of the Cushing's disease. If there was evidence suggesting relapse, a low-dose dexamethasone suppression test was performed. In many patients, sequential collections of early morning urine specimens for urinary cortisol to creatinine ratio were also performed in an attempt to diagnose cyclical and intermittent forms of recurrent hypercortisolism. We did this if there was conflicting endocrine data, or if patients were slow to lose abnormal clinical features.
Mean age at diagnosis was 40.3 years (range 14-70 years). Mean follow-up up time was 9.6 years (range 1-21 years). Forty-five patients (9 males/36 females) achieved apparent remission immediately after surgery and were subsequently studied long term. Of these 45 patients, four have subsequently died while in remission from hypercortisolism. Ten of the remaining 41 patients have relapsed. Of those 10, six demonstrated definite cyclical cortisol secretion. Two of the 10 had undetectable basal serum cortisol levels in the immediate postoperative period. Thirty-one patients are still alive and in remission. Fourteen (45%) of the 31 who remained in remission had detectable serum cortisol levels (> 50 nmol/l) immediately postoperatively, and remain in remission after a mean of 8.8 years. Our relapse rate was therefore 10/45 (22%), after a mean follow-up time of 9.6 years, with mean time to relapse 5.3 years.
The overall remission rate of 56% (35/63) at 9.6 years follow-up is disappointing and merits some re-appraisal of the widely accepted principle that pituitary surgery must be the initial treatment of choice in pituitary-dependent Cushing's syndrome. Following pituitary surgery, careful ongoing expert endocrine assessment is mandatory as the incidence of relapse increases with time and also with increasing rigour of the endocrine evaluation. A significant number of our patients were shown to have relapsed with a cyclical form of hypercortisolism.
Clinical Endocrinology 11/2005; 63(5):549-59. · 3.17 Impact Factor
ABSTRACT: To assess the feasibility and practicalities of using the technique of mental practice as an adjunct in the rehabilitation of the upper limb following stroke.
A series of single-case studies.
A stroke rehabilitation unit in Belfast.
Fourteen patients admitted for rehabilitation of their first stroke: six men and four women, aged 45-81 between 10 and 176 days post stroke.
Each patient underwent a single-case design, with two weeks baseline, two weeks intervention and one week withdrawal. The intervention consisted of structured daily mental practice sessions of a reach and grasp task, in addition to their usual therapy.
The upper limb component of the Motricity Index was used to grade motor activity sequentially across the timescale of the study.
Of the 14 patients recruited, four withdrew and 10 completed the study. Nine showed improvement in upper limb Motricity Index score with mental practice as measured by the two-band standard deviation method. One of these cases demonstrated an unstable baseline such that changes could not be attributed to intervention.
This pilot study suggests that mental practice may be useful as an adjunct to physiotherapy after stroke.
Clinical Rehabilitation 03/2004; 18(1):60-8. · 2.12 Impact Factor
ABSTRACT: The presence and biological significance of circulating glycated insulin has been evaluated by high-pressure liquid chromatography (HPLC), electrospray ionization mass spectrometry (ESI-MS), radioimmunoassay (RIA), receptor binding, and hyperinsulinemic-euglycemic clamp techniques. ESI-MS analysis of an HPLC-purified plasma pool from four male type 2 diabetic subjects (HbA(1c) 8.1 +/- 0.2%, plasma glucose 8.7 +/- 1.3 mmol/l [means +/- SE]) revealed two major insulin-like peaks with retention times of 14-16 min. After spectral averaging, the peak with retention time of 14.32 min exhibited a prominent triply charged (M+3H)(3+) species at 1,991.1 m/z, representing monoglycated insulin with an intact M(r) of 5,970.3 Da. The second peak (retention time 15.70 min) corresponded to native insulin (M(r) 5,807.6 Da), with the difference between the two peptides (162.7 Da) representing a single glucitol adduct (theoretical 164 Da). Measurement of glycated insulin in plasma of type 2 diabetic subjects by specific RIA gave circulating levels of 10.1 +/- 2.3 pmol/l, corresponding to approximately 9% total insulin. Biological activity of pure synthetic monoglycated insulin (insulin B-chain Phe(1)-glucitol adduct) was evaluated in seven overnight-fasted healthy nonobese male volunteers using two-step euglycemic-hyperinsulinemic clamps (2 h at 16.6 micro g x kg(-1) x min(-1), followed by 2 h at 83.0 micro g x kg(-1) x min(-1); corresponding to 0.4 and 2.0 mU x kg(-1) x min(-1)). At the lower dose, the exogenous glucose infusion rates required to maintain euglycemia during steady state were significantly lower with glycated insulin (P < 0.01) and approximately 70% more glycated insulin was required to induce a similar rate of insulin-mediated glucose uptake. Maximal responses at the higher rates of infusion were similar for glycated and control insulin. Inhibitory effects on endogenous glucose production, insulin secretion, and lipolysis, as indicated by measurements of C-peptide, nonesterified free fatty acids, and glycerol, were also similar. Receptor binding to CHO-T cells transfected with human insulin receptor and in vivo metabolic clearance revealed no differences between glycated and native insulin, suggesting that impaired biological activity is due to a postreceptor effect. The present demonstration of glycated insulin in human plasma and related impairment of physiological insulin-mediated glucose uptake suggests a role for glycated insulin in glucose toxicity and impaired insulin action in type 2 diabetes.
Diabetes 02/2003; 52(2):492-8. · 8.29 Impact Factor