A trout fisherman with hypercalcaemia and skin lesions.

A 67-year-old trout fisherman presented with a six-week history of polyuria, polydipsia, dyspnoea on exertion and the development of subcutaneous extensor surface skin nodules. He was hypercalcaemic with acute renal impairment. Parathyroid hormone was suppressed and vitamin D levels were within normal limits. The patient had a past history of hypothyroidism, but thyroid replacement was adequate. Hypoadrenalism, myeloma and metastatic malignancy were excluded. Biopsy of a subcutaneous nodule revealed dermally based non-caseating granulomata, consistent with sarcoidosis. Serum angiotensin-converting enzyme was elevated, and computerized tomography scanning of the chest and abdomen revealed widespread lymphadenopathy with multiple lung nodules and splenomegaly. Prednisolone therapy produced rapid resolution of his skin lesions and normalization of his bone and renal biochemistry. The mechanism of hypercalcaemia in sarcoidosis is poorly understood but is thought to involve parathyroid hormone-independent 1-hydroxylation of 25-hydroxyvitamin D within sarcoid lesions. This process may be exacerbated by exposure to UV light and it is of interest that this patient developed symptoms after a period of intense trout fishing in the good weather of April and May 2007.

Atypical presentation of infiltrative thyroid dermopathy.

A 46-year-old woman with Graves' disease developed infiltrative dermopathy of the thenar eminences. We believe this to be the first reported case of infiltrative dermopathy affecting the thenar eminences, and question whether repetitive occupational injury may have been a contributing factor. There is little published evidence to guide the treatment of infiltrative dermopathy.

Implementing a national quality assurance system for diabetes care: the Scottish Diabetes Survey 2001-2006.

AIM: To create a standardized systematic quality assurance system for diabetes care throughout Scotland. METHODS: Each of 15 National Health Service (NHS) boards have submitted core diabetes data for a nationally agreed data specification on an annual basis since 2001. These data are collated to produce an annual national report. We describe the iterative progress of the work in obtaining and analysing this information. The setting was Scotland, with a population of 5 million. RESULTS: In Scotland in 2006, 196,801 people (3.9% of the population) were reported as having diabetes compared with 105,777 in 2001. In 2006 the prevalence of reported diabetes varied from 3.5 to 4.4% in different NHS board areas, reflecting variation in completeness of local registers as well as different demographic patterns. The completeness of recording of many clinical parameters has also increased. (2002 data n = 103,755: diagnosis date 77%, HbA(1c), blood pressure and cholesterol within 15 months 71, 67 and 60%, respectively, increasing to 98, 87, 89 and 85% by 2006, n = 196,801.) A national information management and technology solution (Scottish Collaborative Information-Diabetes Care), involving automatic daily collection of data from routinely used systems both in primary and secondary care, is now used to co-ordinate the collection of data in all NHS board areas. CONCLUSIONS: We have used routine data to estimate the prevalence of reported diabetes in Scotland, UK. This iterative approach to quality improvement has taken 6 years to achieve a baseline measure of care. There is potential to analyse these data further for a better understanding of the epidemiology of diabetes in Scotland. The national diabetes information technology system will contribute to this process.

Risk stratification in acute coronary syndromes--does the TIMI risk score work in unselected cases?

BACKGROUND: Management of patients with an acute coronary syndrome (ACS) requires accurate risk stratification to guide appropriate therapy. AIM: To assess the utility of the TIMI risk score in stratifying patients with possible ACS in routine clinical practice. DESIGN: Prospective observational study. METHODS: We recruited 869 consecutive patients with a diagnosis of possible ACS attending the acute medical receiving unit of a district general hospital. The main outcome measures were recurrent myocardial infarction, urgent revascularization, and all-cause mortality. TIMI risk score was calculated for each patient, and each was also assigned a risk group based on electrocardiogram (ECG) changes and troponin levels only. After follow-up, Cox univariate and multivariate regression was used to evaluate the influence of potential risk factors on duration of event-free survival, and likelihood ratio tests to assess the fit of the models. RESULTS: Increasing TIMI risk score was associated with increased risk of events (p<0.001), as was higher risk group from ECG plus troponin stratification (p<0.001). The likelihood ratio comparison favoured the TIMI risk score (difference 13.910, 5 degrees of freedom, p = 0.016). DISCUSSION: The TIMI risk score is a valid tool for risk stratification in unselected cases with possible acute coronary syndrome. It is superior to ECG changes and troponin alone, although this simpler method also achieves good risk stratification.

Appropriateness of bed usage for inpatients admitted as emergencies to internal medicine services.

OBJECTIVE: To establish the appropriateness of bed usage for acute care within the medical directorates of two district general hospitals using a validated assessment tool, the Emergency Admission Review (EAR). This tool assesses the appropriateness of day of care against strict criteria and allows classification of care as either acute or non-acute. DESIGN: Prospectively, 200 medical emergency admissions, 100 in each of the hospitals, were selected. Following identification patients were assessed every two days during the first fortnight of admission or until discharge. Those patients staying longer than two weeks were then assessed weekly until conclusion of the audit period or discharge whichever was reached first. SETTING: The medical directorates of two District General Hospitals within one acute NHS trust. SUBJECTS: All patients admitted as medical emergencies, who were 14 years or older and had a length of stay of 24 hours or more. RESULTS: A total of 787 acute in-patient bed days were analysed in Hospital A of which 363 (46%) were deemed inappropriate for acute care. In Hospital B 810 bed days were analysed and 44% (363) were deemed inappropriate. In Hospital A the most common reason for bed-days not meeting the acute care criteria was short-term waiting, accounting for 60% (217 days) of the total bed days deemed non-acute. In Hospital B the most common reason for patients receiving non-acute care was that they were having active rehabilitation. This accounted for 29% (105 days) of the total number of non-acute care days. In Hospital B three patients accounted for 28% of the total occupied bed days. CONCLUSIONS: The use of the EAR is a systematic and objective approach to the assessment of appropriateness of acute care. It applies strict criteria to determine the reason for a patient's continued hospital stay. From the results it is clear that a significant proportion of medical emergency admissions in both Hospital A and B remain in hospital for care that is deemed non-acute and therefore in theory could be performed in another setting. This information has significant potential in identifying the opportunities for streamlining services within hospitals to reduce short-term delays and also to inform the development of intermediate care services both within and outwith the acute hospital setting.

Potentiation of the hypoglycaemic response to glipizide in diabetic patients by histamine H2-receptor antagonists.

In a randomised placebo controlled study, two groups of six maturity onset diabetic patients stabilised on glipizide were given cimetidine (400 mg) or ranitidine (150 mg) 3 h before a standardised meal. In comparison with placebo, both cimetidine and ranitidine significantly reduced the post-prandial rise in blood glucose by a mean of 40% and 25% respectively producing glucose levels of less than 3 mmol l-1 (lowest 1.5 mmol l-1) in four patients. Both drugs also significantly increased plasma glipizide AUC by approximately 20%. Caution should be exercised when initiating treatment with H2-receptor antagonists in diabetics receiving sulphonylurea hypoglycaemic agents.

Wolfram (DIDMOAD) syndrome: a complex long-term problem in management.

We describe five patients with Wolfram syndrome (diabetes insipidus, diabetes mellitus, optic atrophy and deafness). Three of the patients appear to have had very gradual onset of diabetes mellitus at an early age yet all patients when tested for C-peptide response to glucagon were severely deficient. All patients are registered blind from primary optic atrophy, two have severe hearing difficulties and three high tone sensorineural hearing loss on audiometry. Four patients have cranial diabetes insipidus which in two cases is partial and of gradual onset and was attributed to poor control of the diabetes mellitus. In one case treatment of the insipidus relieved enuresis. All five patients have evidence of dilatation of the urinary tract and one patient is managed in the long-term by self-catheterisation which has resulted in one episode of bacteraemia. One patient has marked testicular atrophy and investigation reveals this to be due to primary hypogonadism and not to hypothalamic-pituitary dysfunction. One female patient had her menarche delayed until the age of 19 years but has subsequently had the only successful pregnancy in a patient with this syndrome of which we are aware.

The effect of cimetidine and ranitidine on serum high density lipoprotein subfractions.

Of the two major subfractions of high density lipoprotein (HDL), HDL2 cholesterol (HDL2-C) and not HDL3 cholesterol (HDL3-C) correlates negatively with coronary heart disease. To study the effect of cimetidine and ranitidine on HDL subfractions, 6 healthy males received cimetidine (600 mg bid) ranitidine (150 mg bid) and placebo (one tab bid) for 1 week each, in random order. Measurements of HDL cholesterol (HDL-C), HDL2-C, HDL3-C were made on day 7 of each week. Comparing cimetidine with placebo, HDL2-C/HDL-C, HDL2-C/total cholesterol and HDL2-C/HDL3-C increased significantly while HDL3-C/HDL-C decreased. There was no difference in HDL-C parameters between ranitidine and placebo. Cimetidine treatment results in redistribution of HDL subfractions in favour of HDL2. The mechanism is not H2-receptor antagonism as ranitidine had no such effect.

The characterization and energetic potential of brown adipose tissue in man.

In adult man, brown fat can be detected in perinephric fat depots by visual inspection, electron microscopy and nucleotide binding to the tissue-specific uncoupling protein. The 32 kDa uncoupling protein is functionally active, showing a nucleotide-sensitive conductance to protons and an uncoupling response to fatty acids. The amount of uncoupling protein in human mitochondria is equivalent to that in a partially cold-adapted guinea pig, indicating some potential for thermogenesis. Respiratory capacity measurements indicate that the total perinephric fat in adult man can only account for one-fivehundredth of the whole-body response to infused noradrenaline. Thus, although brown fat has been found to be quantitatively important in animal studies, considerable caution must be exercised in extrapolating its significance to adult man.

The clinical and metabolic responses to early surgical treatment for hyperthyroid Graves' disease: a comparison of three pre-operative treatment regimens.

We have compared the clinical and metabolic responses of three groups of patients undergoing subtotal thyroidectomy for hyperthyroid Graves' disease. These patients were prepared for surgery with propranolol alone, propranolol plus potassium iodide or the long acting beta-adrenoceptor antagonist nadolol plus potassium iodide. Pre-treatment with potassium iodide reduced serum T4 to normal or subnormal in all patients. Patients in the propranolol group had significantly higher pulse rates and temperatures after operation and one patient developed an exacerbation of the hypermetabolic state. The perioperative rise in serum cortisol and blood glucose was delayed in patients in the propranolol group and this was also noted in one severely hyperthyroid patient on propranolol + potassium iodide. Nadolol was administered once daily as compared to multiple daily doses with propranolol. Despite this, plasma nadolol levels were consistently higher throughout the perioperative period while propranolol levels in patients on both propranolol alone and propranolol + potassium iodide were highly variable and sometimes undetectable. We conclude that, in the rapid preparation of patients with hyperthyroid Graves' disease for surgery, the combination of nadolol + potassium iodide has significant advantages over the other two regimens.

The effect of chronic treatment with a non-selective beta-adrenoceptor antagonist on the enteroinsular axis and intermediary metabolites.

In a single-blind randomized placebo-controlled cross-over study in hypertensive patients we have examined the effects of treatment with the non-selective beta-adrenoceptor antagonist nadolol on the responses of glucose, intermediary metabolites and the hormones of the enteroinsular axis to the ingestion of a mixed meal. During treatment with nadolol the plasma insulin concentration 30 min after ingesting the meal was significantly lower than on placebo and the plasma glucose rose more slowly. Plasma concentrations of GIP tended to be higher during nadolol than placebo treatment. No significant effects of treatment with nadolol were noted on pancreatic glucagon or intermediary metabolites.

Cortisol and dexamethasone elimination during treatment with cimetidine.

In a randomised cross-over study of treatment for 7 days with cimetidine 600 mg twice daily and placebo, cimetidine had no effect on the pharmacokinetics of a single intravenous dose of dexamethasone sodium phosphate. Likewise the elimination characteristics of endogenous cortisol in the dexamethasone suppressed state were not affected by cimetidine.

Beta adrenoceptor blockade and responses of serum lipids to a meal and to exercise.

During a randomised placebo controlled trial of the effects of nadolol in hypertensive patients serum lipid profiles were obtained while the patients were fasting and during and after a meal and an exercise test. Treatment with nadolol was associated with a significant reduction in high density lipoprotein cholesterol at all time points. Serum triglyceride concentrations during treatment with nadolol were higher in the fasting state, though not significantly so, increased further postprandially, and were significantly higher during and after exercise. The changes in high density lipoprotein cholesterol and triglyceride concentrations during beta adrenoceptor blockade may be secondary to a reduction in lipoprotein lipase activity.