Lesson of the week. Are spontaneous hypoglycaemia, raised plasma insulin and C peptide concentrations, and abnormal pancreatic images enough to diagnose insulinoma?
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Adult↗
Biomedical subjects
P Perros
Publications and source records attributed to P Perros.
Hospital management of diabetic ketoacidosis: are clinical guidelines implemented effectively?
A study was undertaken in order to examine the quality of management of diabetic ketoacidosis (DKA) in a teaching hospital and to assess whether the introduction of clinical guidelines contributed to a satisfactory outcome. Data on presentation and management of 71 cases of DKA admitted in one calendar year (1994) were collected and analysed. Comparing the data to standards set in guidelines, inadequacies of clinical management were identified including delay in initiation of intravenous fluid replacement (greater than 30 min) and intravenous insulin (greater than 60 min) in 70% and 69% of cases, respectively; under-replacement with intravenous fluid in the first 24 h (less than 6.5 l) in 70% of cases, and insufficient intravenous potassium replacement (less than 70 mmol) in the first 24 h in 70% of cases. Suboptimal management of DKA may have contributed towards death in one of the three fatalities, and to morbidity in other patients. In 22.5% of cases (group 1) in whom the guidelines were alleged to have been followed, intravenous fluid, potassium, and insulin had been administered earlier and in larger quantities compared to the remaining cases (group 2). However, in most cases in group 1 the standards set by the guidelines were unfulfilled and the incidence of hypokalaemia, hypoglycaemia, and duration of in-patient stay did not differ from group 2. The treatment of DKA by non-specialist general medical staff in a large teaching hospital was frequently inadequate and was associated with significant mortality and morbidity. The introduction of guidelines had moderately influenced the process of managing DKA but not the outcome, probably because of the low rate of their implementation by junior doctors.
Adolescent↗
The long-term sequelae of severe hypoglycemia on the brain in insulin-dependent diabetes mellitus.
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Brain↗
Brain abnormalities demonstrated by magnetic resonance imaging in adult IDDM patients with and without a history of recurrent severe hypoglycemia.
OBJECTIVE: Previous studies of a cohort of 100 patients with IDDM have shown that a history of recurrent severe hypoglycemia is associated with a modest impairment of cognitive function. The aim of the present study was to determine whether IDDM patients with and without a history of severe hypoglycemia have lesions in the brain that are identifiable by magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) and to investigate the putative relationship of any structural brain abnormalities with cognitive function. RESEARCH DESIGN AND METHODS: MRI and MRS of the brain were performed in 22 patients from the original cohort. Eleven IDDM patients with no history of severe hypoglycemia (group A) were compared with 11 IDDM patients who had a history of five or more episodes of severe hypoglycemia (group B). RESULTS: Nine patients (41%) had abnormal scans. Two types of abnormalities were observed: high-intensity rounded lesions, > 3 mm in diameters, distributed in the periventricular white matter (leukoaraiosis) in four patients; and cortical atrophy in five patients. Five patients in group B had cortical atrophy, whereas no patient in group A demonstrated this feature (P < 0.05). MRS of the frontal and parietal lobes showed no differences in the N-acetyl aspartate/creatine or N-acetyl aspartate/choline ratios between groups A and B. Patients with cortical atrophy showed a nonsignificant trend toward reduced performance on Rapid Visual Information Processing. CONCLUSIONS: Brain abnormalities demonstrated by MRI are common in patients with IDDM of long duration and are suggestive of premature aging of the brain. IDDM per se may be an important pathogenic factor, but a significant association was observed between a history of recurrent severe hypoglycemia and cortical atrophy, which may be related to the modest impairment of cognitive function that has been reported previously.
Adult↗
An audit of waiting times in the diabetic outpatient clinic: role of patients' punctuality and level of medical staffing.
A survey of patients' waiting times was performed in the follow-up clinics of a large hospital outpatient diabetic department (approximately 6500 patients). Over a period of 1 week, 138 patients attended 5 review outpatient clinics. The overall patient:doctor ratio was 11.1:1. Only 18.8% of patients were seen by the doctor, and 86% by the nurse within 30 min of their appointment time. A policy of strict adherence to the formal appointment times was implemented but had no effect on the waiting time (20% of patients were seen by the doctor, and 82.2% by the nurse within 30 min of their appointment time). The combined effects of adherence to actual appointment times and increasing the number of doctors (lowering the patient:doctor ratio to 7.7:1), reduced the total waiting times, and increased the proportion of patients seen by the doctor or nurse within 30 min of their appointment time, to 31% and 100%, respectively. Strict adherence to appointment times was difficult to implement and ineffective but the patient:doctor ratio was important in determining waiting times in the diabetic clinic. Inadequate medical staffing of diabetic outpatient clinics is a major cause of prolonged waiting time for patients. This approach may be useful in assessing and improving the organizational efficiency of a diabetes service.
Ambulatory Care Facilities↗
Non-islet cell tumour-associated hypoglycaemia: 111In-octreotide imaging and efficacy of octreotide, growth hormone and glucocorticosteroids.
A patient presented with frequent episodes of spontaneous hypoglycaemia due to a solitary fibrous tumour of pleural origin, secreting incompletely processed pro-insulin-like growth factor II (big IGF-II). Somatostatin receptors were demonstrated in the tumour by 111 inlabelled octreotide scintigraphy, but despite maximal doses of octreotide, there was no suppression of big IGF-II secretion and the hypoglycaemia persisted. The combination of GH and glucocorticoid therapy abolished the hypoglycaemia.
Aged↗
Altered taste sensation in newly-diagnosed NIDDM.
OBJECTIVE: To assess gustatory appreciation in newly diagnosed NIDDM patients and to determine whether it altered with the improvement of glycemic control after treatment with diet and oral hypoglycemic drugs. RESEARCH DESIGN AND METHODS: Assessments of taste, peripheral and autonomic neural function, diet, and oral microbiological flora were performed in 20 patients before and after treatment of hyperglycemia, 20 matched nondiabetic control subjects, and 11 patients with long duration of diabetes and advanced peripheral neuropathy. RESULTS: Median total HbA1 fell from 12.6 to 8.8% in new diabetic patients after 3-5 months of treatment. Electrical taste thresholds, detection threshold for glucose, and recognition threshold for glucose and salt were increased in newly-diagnosed NIDDM patients compared with the control subjects. The dose-response curve to glucose (using a visual analogue scale [VAS]) of newly-diagnosed NIDDM patients was significantly impaired and improved after treatment. By contrast, newly-diagnosed NIDDM patients had normal VAS taste responses to fructose, salt, and urea. Measurements of somatic and autonomic nerve function did not correlate with electrical or chemical taste function. CONCLUSIONS: Newly-diagnosed NIDDM patients have a blunted taste response, which displays a degree of specificity to glucose, is partially reversed after correction of hyperglycemia, and is independent of somatic or autonomic nerve function. This taste abnormality may influence the premorbid choice of nutrients, with a preference for sweet-tasting foods, thereby exacerbating hyperglycemia.
Autonomic Nervous System Diseases↗
Acute challenge ERP as a prognostic of stimulant therapy outcome in attention-deficit hyperactivity disorder.
Thirty-five children were tested with an auditory oddball P300 paradigm both before and 2 hr after a single-dose trial of methylphenidate (MPH). A prediction of the long-term benefit of medication was then made based on the magnitude of the acute changes in P3b amplitude. Those with postdrug amplitude increases of at least 30% were predicted to respond favorably to stimulants. All children were followed-up at 6 months. The original MPH Challenge Test predictions (based on acute post drug P3b amplitude changes) were then compared with the clinicians' evaluations of outcome. The MPH challenge classification accurately predicted outcome in 81% of cases.
Acoustic Stimulation↗
Thyroid-associated ophthalmopathy: pathogenesis and clinical management.
The pathogenesis of thyroid-associated ophthalmopathy is autoimmune. The questions to which answers are eagerly awaited are the identification of the autoantigen(s) and the definition of the autoimmune processes (cellular or humoral) responsible. Cellular and humoral immune responses and modulation by cytokines, against orbital tissues have been described. A link between the thyroid and the orbit seems inevitable, possibly in the form of a cross-reactive antigen, and top of the list of candidate antigens is the TSH receptor. Optimal treatment of TAO necessitates careful assessment. Thoughtful planning and timing and choice of intervention with conventional therapies, can lead to satisfactory results in the majority of cases. In addition to treating the severe complications, such as optic neuropathy, corneal exposure and muscle misalignment, corrective surgery to reconstruct the appearance of the patient's eyes should be made available.
Adult↗
Natural history of thyroid associated ophthalmopathy.
BACKGROUND: The natural history of thyroid associated ophthalmopathy is poorly documented, although it is widely thought that many cases improve spontaneously with time. This has important implications in the management of patients and is also a critical factor when assessing the effects of different treatments. OBJECTIVE: To document the natural history of thyroid associated ophthalmopathy, 59 patients were studied longitudinally and the severity of eye disease documented at regular intervals. METHODS: Fifty-nine patients with thyroid associated ophthalmopathy who had not received immunosuppressive or surgical treatment for their eye disease, were recruited from a combined thyroid-eye clinic. They were assessed at presentation and at 3-6-monthly intervals for a median of 12 months. The eyes were assessed by separate and objective measurements relating to the status of the eyelids, cornea, extraocular muscles, proptosis and optic nerve function. In addition, a scoring system based on the above measurements was used to grade the overall severity of eye disease. RESULTS: Thirteen patients (22%) improved substantially, 25 patients (42.4%) showed minor improvement, 13 patients (22%) did not change, and 8 patients (13.5%) deteriorated progressively, to the extent that immunosuppressive treatment was considered to be necessary. CONCLUSIONS: A significant proportion of patients with thyroid associated ophthalmopathy (64.4% in the present series) improve spontaneously so serial assessment plays an important part in deciding which patients require immunosuppressive treatment. These findings also support the view that clinical trials designed to test the efficacy of new treatments in thyroid associated ophthalmopathy should be scrupulously controlled to allow for the natural tendency towards remission.
Adolescent↗
Frequency of thyroid dysfunction in diabetic patients: value of annual screening.
A randomly selected group of 1310 adult diabetic patients attending a diabetic outpatient clinic received annual screening for thyroid disease, by estimating serum free thyroxine and TSH concentrations. The overall prevalence of thyroid disease was found to be 13.4%, and was highest (31.4%) in Type 1 diabetic females, and lowest in Type 2 diabetic males (6.9%). As a direct result of screening, new thyroid disease was diagnosed in 6.8% (89 patients) of the population screened; the commonest diagnosis was subclinical hypothyroidism (4.8%), followed by hypothyroidism (0.9%), hyperthyroidism 0.5%), and subclinical hyperthyroidism (0.5%). Female patients with Type 1 diabetes had the highest annual risk of developing thyroid disease (12.3%), but all patient groups had a higher incidence of thyroid dysfunction, compared to that reported in the general population. This study suggests that thyroid function should be screened annually in diabetic patients to detect asymptomatic thyroid dysfunction which is increased in frequency in a diabetic population.
Adult↗
Demonstration of thyrotropin binding sites in orbital connective tissue: possible role in the pathogenesis of thyroid-associated ophthalmopathy.
The thyrotropin (TSH) receptor is implicated in the pathogenesis of thyroid-associated ophthalmopathy, but its presence has not been demonstrated in orbital tissues. Binding of 125I-TSH to porcine orbital connective tissue and thyroid membranes was studied. At pH 7.4 125I-TSH bound to thyroid membranes with high affinity, but not to orbital connective tissue membranes. At pH 5.2, binding of 125I-TSH was evident on thyroid and orbital connective tissue membranes, although of low affinity. Low affinity binding at pH 5.2, could also be demonstrated on orbital fibroblasts; binding to membranes prepared from extraocular muscle, or from abdominal adipose tissue was not detected. Immunoglobulin G from healthy subjects (n = 17) and patients with ophthalmopathy (n = 19) were tested for inhibition of 125I-TSH binding to membranes. As anticipated patients' IgG exhibited greater inhibition than normal controls with thyroid membranes at pH 7.4 (p < 0.001). Similar results were obtained with thyroid membranes (p < 0.05), and orbital connective tissue membranes at pH 5.2 (p < 0.001). Significant correlations were found when percentage inhibition by IgG was compared between: thyroid membranes at pH 7.4 and thyroid membranes at pH 5.2, orbital connective tissue membranes at pH 5.2 and thyroid membranes at pH 7.4, and orbital connective tissue membranes at pH 5.2 and thyroid membranes at pH 5.2. A low affinity TSH-binding site is present in orbital connective tissue, and is recognized by IgG's from patients with ophthalmopathy which suggests that TSH receptor antibodies may target the orbit.
Adolescent↗
Anti-mitochondrial antibodies in patients with Graves' disease may not signify primary biliary cirrhosis.
Two patients with Graves' disease were incidentally found to have anti-mitochondrial antibodies by immunofluorescence in the absence of symptoms, clinical signs or biochemical evidence of liver dysfunction. Anti-mitochondrial antibody titres became undetectable in both patients on follow-up. Screening of the patients' sera by immunoblotting against the purified antigens of the M2 complex was negative. We conclude that in these cases, anti-mitochondrial antibodies detected by immunofluorescence were directed against antigens other than the primary biliary cirrhosis-associated M2 complex and therefore did not signify subclinical primary biliary cirrhosis.
Adolescent↗
Chronic pontine dysfunction following insulin-induced hypoglycemia in an IDDM patient.
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Adult↗
Age and gender influence the severity of thyroid-associated ophthalmopathy: a study of 101 patients attending a combined thyroid-eye clinic.
BACKGROUND: The pathogenesis of thyroid-associated ophthalmopathy is thought to be autoimmune, although environmental and genetic factors are also considered to be important. As the morbidity of thyroid-associated ophthalmopathy is considerable and treatment often unsatisfactory, there a need to identify possible predisposing factors. OBJECTIVE: The study was undertaken in order to ascertain the relationship between age, gender and severity of thyroid-associated ophthalmopathy. PATIENTS: One hundred and one consecutive patients with thyroid-associated ophthalmopathy who presented over a period of 5 years to a combined thyroid-eye clinic. METHODS: Patients were assessed by grading their inflammatory signs and degree of diplopia, and by measurement of exophthalmos, palpebral aperture, differential intraocular pressure, and visual acuity. On the basis of the above an ophthalmopathy index was devised to grade the overall severity of eye disease. RESULTS: The mean age was 49.2 years (SD 13.4), the female-to-male ratio was 4.05, and mean ophthalmopathy index 6.49 (SD 3.3). Optic nerve compression was present in 9.9% of patients. There was a positive relationship between age and ophthalmopathy index (P < 0.001); after correcting for age, males had an average ophthalmopathy index 41% greater than that of females. CONCLUSION: There is an association between severity of thyroid-associated ophthalmopathy and (i) advancing age and (ii) female-to-male ratio, which has not been previously described. Patients over the age of 60 (particularly males) with Graves' disease appear to be at risk of developing severe eye disease.
Age Factors↗
Autoantibodies to IGF-1 binding sites in thyroid associated ophthalmopathy.
Graves' disease is an autoimmune disorder but the nature of the association between hyperthyroidism and ophthalmopathy is not yet understood. Serum autoantibodies to orbital tissues have previously been identified and the cross-reactivity with orbital and thyroid antigens has been implicated in the development of thyroid-associated ophthalmopathy (TAO). The ophthalmopathy of Graves' disease is remarkable for the hypertrophy of extraocular muscles and proliferation of fibroblasts within the orbit; features which suggest a possible involvement of growth factors. The present study was therefore undertaken to investigate the interaction of IgGs extracted from the sera of patients with Graves' disease, with or without overt ophthalmopathy, with respect to IGF-1 receptor binding sites on fibroblasts from human orbital tissue. IGF-1 binding sites were demonstrated on human orbital fibroblast monolayers grown from eye muscle explants. These cells exhibited a population of high affinity IGF-1 binding sites (Kd, 0.5nM SEM +/- 0.05). IgG prepared from sera taken from patients with Graves' disease (n = 23) significantly inhibited [125I]IGF-1 binding to orbital fibroblasts when compared to IgGs prepared from normal volunteers (n = 13, p < 0.002). It was found that 12 of 23 (52%) patients' IgG samples gave rise to significant levels of inhibition of [125I]IGF-1 binding to orbital fibroblasts. The IgG preparations did not bind directly to IGF-1. This study demonstrates that IgG prepared from patients with Graves' disease with or without overt ophthalmopathy interact with IGF-1 binding sites on orbital fibroblasts whereas IgG from normal subjects had no significant effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Antibody Specificity↗
Octreotide and Graves' ophthalmopathy.
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Graves Disease↗
Power spectral EEG analysis and EEG variability in obsessive-compulsive disorder.
Spectral EEG characteristics of thirteen patients with severe Obsessive-Compulsive Disorder (OCD) were investigated topographically. The finding of predominantly left posterior frontal to mid-temporal theta-2 is discussed in light of previous EEG studies and recent neuroradiologic findings.
Adult↗