Adopting seven-day working in practice: a report by the Royal College of Physicians and Surgeons of Glasgow.

Following the UK Academy of Medical Royal Colleges Report on seven day consultant present care, the Royal College of Physicians and Surgeons of Glasgow held a symposium to explore clinicians' views on the ways in which clinical care should best be enhanced outside 'normal' working hours. In addition, a survey of members and fellows was undertaken to identify the tests which would make the greatest impact on care out of hours. Key messages were: (a) that seven-day consultant delivered care would not achieve the desired benefit to patient care if introduced in isolation from other inter-relating factors. These include alternatives to hospital admission, enhanced nursing support, increased junior medical, pharmacy, social care and ambulance availability and greater access to selected diagnostic services; (b) that the care of hospital inpatients is a service which is one part of the totality of secondary care provision. Any significant change in the deployment of staff for inpatient care must be carefully managed so as not to result in a reduced quality of care provided by the rest of the system.

Insulin resistance in type 1 diabetes: what is 'double diabetes' and what are the risks?

In this review, we explore the concept of 'double diabetes', a combination of type 1 diabetes with features of insulin resistance and type 2 diabetes. After considering whether double diabetes is a useful concept, we discuss potential mechanisms of increased insulin resistance in type 1 diabetes before examining the extent to which double diabetes might increase the risk of cardiovascular disease (CVD). We then go on to consider the proposal that weight gain from intensive insulin regimens may be associated with increased CV risk factors in some patients with type 1 diabetes, and explore the complex relationships between weight gain, insulin resistance, glycaemic control and CV outcome. Important comparisons and contrasts between type 1 diabetes and type 2 diabetes are highlighted in terms of hepatic fat, fat partitioning and lipid profile, and how these may differ between type 1 diabetic patients with and without double diabetes. In so doing, we hope this work will stimulate much-needed research in this area and an improvement in clinical practice.

A pilot study for presence of circulating tumour cells in adenoid cystic carcinoma.

Adenoid cystic carcinoma (ACC) is a rare salivary gland neoplasm with a poor long-term prognosis due to multiple recurrences and distant metastatic spread. Circulating tumour cells (CTCs) are tumour cells shed from a primary, recurrent, or metastatic cancer that are detectable in the blood or lymphatics. There is no literature to date confirming the presence of CTCs in ACC. The aim of this study was to determine whether CTCs are detectable in ACC. Blood samples were collected from eight patients with histologically confirmed ACC. The TNM stage of the tumour was recorded, as well as any prior treatment. CTCs were isolated by spiral microfluidics and detected by immunofluorescence staining. Three of the eight patients recruited (32.5%) had staining consistent with the presence of CTCs. Of these three patients with detectable CTCs, one had confirmed pulmonary metastasis, one had suspected pulmonary metastasis and was awaiting confirmation, and one had local recurrence confirmed on re-resection. One patient with known isolated pulmonary metastasis had previously undergone a lung metastasectomy and did not have CTCs detected. CTCs are detectable in ACC. In this small patient sample, CTCs were found to be present in those patients with recurrent local disease and known distant metastatic disease. CTCs in ACC should be investigated further for their potential use as an adjunct in staging, prognosis, and the detection of recurrence.

Functional dissociations between subregions of the medial prefrontal cortex on the rodent touchscreen continuous performance test (rCPT) of attention.

Converging evidence in humans, monkeys, and rodents suggests a functional dissociation of cognitive function along the dorso-ventral axis of the prefrontal cortex (PFC). Previous studies of attention suggest that the anterior cingulate cortex (ACC) plays a role in target detection, whereas the prelimbic (PL) cortex is important for tests requiring the combined detection and discrimination of signals. We investigated the effect of discrete, quinolinic acid-induced lesions of subregions of the rat medial PFC (mPFC)-ACC, PL cortex, and infralimbic (IL) cortex-on attentional performance on the recently developed rodent touchscreen continuous performance test (rCPT). Rats were tested under a range of behavioral conditions involving stimulus duration (SD), flanker distraction, temporal predictability, and event rate. Rats with lesions of the PL cortex demonstrated the most persistent attentional impairment under conditions of reduced and variable SD and high event rate (lower discrimination sensitivity [d'] and hit rate), and flanker distraction (lower hit rate). Rats with lesions of the ACC exhibited a profound but transient attentional impairment (lower d' and hit rate) in the early stages of behavioral testing, which ameliorated with repeated testing. Rats with lesions of the IL cortex showed no impairments on response control measures. The PL cortex plays a greater role than the ACC in the detection and discrimination of a complex visual stimulus among multiple nontarget stimuli in the rCPT. The findings support evidence for a functional dissociation of attentional performance along the dorso-ventral axis of the mPFC. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Pregnancy and childbirth after an iliac crest free flap.

We report two successful pregnancies and vaginal deliveries by patients who had previously had deep circumflex iliac artery free flaps that had been harvested for reconstruction in the head and neck.

Cardiac troponin I concentrations in people presenting with diabetic ketoacidosis.

BACKGROUND: Elevated troponin concentrations may be observed in a wide spectrum of medical disorders in people without evidence of overt ischaemic heart disease. The prospective relationship between serum cardiac troponin I (cTnI) and diabetic ketoacidosis (DKA) has not been examined in adults. METHODS: Forty patients (14 male and 26 female) with type 1 diabetes were recruited. cTnI, creatine kinase (CK), cystatin C and beta-hydroxybutyrate were measured on admission and at 24, 48 and 72 h post-admission. Daily electrocardiographs were also performed. RESULTS: Four out of forty subjects presenting with DKA had an increase in cTnI (median (SD) 0.06 (0.31) microg/L). One of the subjects had multiple possible reasons for the elevated cTnI concentration. However, the other three subjects had no obvious precipitating factors. This cohort underwent echocardiography and thallium-201 scintigraphy, which revealed no abnormalities. CONCLUSIONS: Minor troponin elevations appear to occur in a small number of subjects with type 1 diabetes presenting with DKA. The clinical relevance of this at this stage remains unknown and further large-scale studies are suggested.

Detecting the Radiative Decay Mode of the Neutron.

Beta decay of the neutron into a proton, electron, and electron antineutrino is occasionally accompanied by the emission of a photon. Despite decades of detailed experimental studies of neutron beta-decay, this rare branch of a fundamental weak decay has never been observed. An experiment to study the radiative beta-decay of the neutron is currently being developed for the NG-6 fundamental physics endstation at the National Institute of Standards and Technology (NIST) Center for Neutron Research (NCNR). The experiment will make use of the existing apparatus for the NIST proton-trap lifetime experiment, which can provide substantial background reduction by providing an electron-proton coincidence trigger. Tests and design of a detector for gamma-rays in the 10 keV to 200 keV range are under development. The need for a large solid-angle gamma-ray detector that can operate in a strong magnetic field and at low temperature has led us to consider scintillating crystals in conjunction with avalanche photodiodes. The motivation and experimental technique will be discussed.

Proposed Measurement of the Beta-Neutrino Correlation in Neutron Decay.

Currently, the beta-neutrino asymmetry has the largest uncertainty (4 %) of the neutron decay angular correlations. Without requiring polarimetry this decay parameter can be used to measure λ (ga/gv ), test Cabibbo-Kobayashi-Maskawa (CKM) unitarity limit scalar and tensor currents, and search for Charged Vector Current (CVC) violation. We propose to measure the beta-neutrino asymmetry coeffcient, a, using time-of-flight for the recoil protons. We hope to achieve a systematic uncertainty of σa / a ≈ 1.0 %. After tests at Indiana University's Low Energy Neutron Source (LENS), the apparatus will be moved to the National Institute of Standards and Technology (NIST) where the measurement can achieve a statistical uncertainty of 1 % to 2 % in about 200 beam days.

Effects of adrenergic blockade on serum potassium changes in response to acute insulin-induced hypoglycemia in nondiabetic humans.

OBJECTIVE: To determine the possible role of adrenergic mechanisms in mediating the fall in serum potassium concentration after intravenous injection of insulin. RESEARCH DESIGN AND METHODS: Eighteen nondiabetic male volunteers, divided into three groups of six subjects, comprised the study. Hypoglycemia was induced by a bolus of short-acting insulin (0.15 U/kg body wt). Six subjects were studied in control conditions, six during alpha-adrenergic blockade with phentolamine, and six during beta-adrenergic blockade with propranolol. RESULTS: In the control group, there was an immediate fall in serum potassium from 4.0 +/- 0.1 to 3.6 +/- 0.1 mM at baseline + 15 min. After the onset of acute hypoglycemia, potassium decreased further in the control group, reaching a lowest concentration of 3.3 +/- 0.1 mM. In the propranolol group, the late decrease in potassium was inhibited, and there were no further changes in serum potassium. During alpha-blockade, there was an exaggerated fall to 2.6 +/- 0.1 mM at 30 min after the onset of hypoglycemia. CONCLUSIONS: The later fall in serum potassium, which occurs after the onset of hypoglycemia, is probably mediated by stimulation of beta-adrenoreceptors, whereas coincidental stimulation of alpha-adrenoreceptors opposes this fall in potassium and may prevent the development of severe hypokalemia in response to acute hypoglycemia.

Symptoms of acute insulin-induced hypoglycemia in humans with and without IDDM. Factor-analysis approach.

OBJECTIVE: This study allocated the symptoms identified during acute hypoglycemia objectively to the autonomic or neuroglycopenic groups of symptoms by the use of factor analysis. RESEARCH DESIGN AND METHODS: Twenty-five nondiabetic subjects, 14 newly diagnosed insulin-dependent diabetic patients, and 16 insulin-dependent diabetic patients with diabetes greater than 4 yr duration were studied. Acute hypoglycemia was induced with insulin (2.5 mU.kg-1 body wt.min-1 i.v.), and symptoms of hypoglycemia were recorded with a seven-point scale at regular time points throughout the studies. Factor analysis of the symptom scores at the time of the acute autonomic reaction with principal component analysis followed by Varimax rotation was used to separate those symptoms that might belong to neuroglycopenic and autonomic groups. RESULTS: Hypoglycemia was induced to a mean +/- SE plasma glucose nadir of 1.3 +/- 0.1 mM in nondiabetic subjects, to 2.0 +/- 0.3 mM in newly diagnosed diabetic patients, and 1.4 +/- 0.2 mM in patients with diabetes of greater than 4 yr duration. The most frequently reported autonomic symptoms were sweating, trembling, and warmness, and the most frequently reported neuroglycopenic symptoms were inability to concentrate, weakness, and drowsiness. Neuroglycopenic symptoms were reported more commonly at the onset of hypoglycemia, which was identified by the development of symptoms. Factor analysis grouped trembling, anxiety, sweating, warmness, and nausea together, and this grouping was labeled an autonomic factor. A second factor was identified that included dizziness, confusion, tiredness, difficulty in speaking, shivering, drowsiness, and inability to concentrate, which was labeled a neuroglycopenic factor. CONCLUSIONS: This study demonstrated the high frequency with which neuroglycopenic symptoms occur at the onset of hypoglycemia and the symptoms that could be used by an individual patient as a warning of the development of acute hypoglycemia, although the rapid reduction of plasma glucose is faster than experienced by the ambulant diabetic patient. Factor analysis assisted with the allocation of symptoms to either the autonomic or neuroglycopenic groupings, but the allocation of some symptoms remained undefined, and care must be taken when assessing symptoms such as hunger, weakness, blurred vision, and drowsiness when comparing the frequency of autonomic versus neuroglycopenic symptoms. To reduce the confusion resulting from the use of different symptom questionnaires in studies of hypoglycemia, a sample questionnaire is presented, the development of which was assisted by our analysis.

Facilitation of spatial working memory performance following intra-prefrontal cortical administration of the adrenergic alpha1 agonist phenylephrine.

RATIONALE: Spatial working memory is dependent on the appropriate functioning of the prefrontal cortex (PFC). PFC activity can be modulated by noradrenaline (NA) released by afferent projections from the locus coeruleus. The coreuleo-cortical NA system could therefore be a target for cognitive enhancers of spatial working memory. Of the three classes of NA receptor potentially involved, the α2 and α1 classes seem most significant, though agents targeting these receptors have yielded mixed results. This may be partially due to the use of behavioural assays that do not translate effectively from the laboratory to the clinical setting. Use of a paradigm with improved translational potential may be essential to resolve these discrepancies. OBJECTIVES: The objective of this study was to assess the effects of PFC-infused α2 and α1 adrenergic receptor agonists on spatial working memory performance in the touchscreen continuous trial-unique non-matching to location (cTUNL) task in rats. METHODS: Young male rats were trained in the cTUNL paradigm. Cannulation of the mPFC allowed direct administration of GABA agonists for task validation, and phenylephrine and guanfacine to determine the effects of adrenergic agonists on task performance. RESULTS: Infusion of muscimol and baclofen resulted in a delay-dependent impairment. Administration of the α2 agonist guanfacine had no effect, whilst infusion of the α1 agonist phenylephrine significantly improved working memory performance. CONCLUSIONS: Spatial working memory as measured in the rat cTUNL task is dependent on the mPFC. Enhancement of noradrenergic signalling enhanced performance in this paradigm, suggesting a significant role for the α1 receptor in this facilitation.

Arginine vasopressin and oxytocin responses to insulin-induced hypoglycemia in type 1 (insulin-dependent) diabetes.

In normal humans, arginine vasopressin and oxytocin are released acutely from the posterior pituitary gland in response to hypoglycemia, and their release may assist counterregulation. The responses of these hormones to insulin-induced hypoglycemia were measured in 16 insulin-dependent diabetic patients with no autonomic neuropathy (8 patients who had been diabetic less than 5 yr and 8 patients who had been diabetic greater than 15 yr) and in 6 normal subjects. The time of the onset of hypoglycemia and the mean blood glucose nadirs were similar in all groups, but the blood glucose recovery was delayed in the diabetic patients. In the normal subjects plasma arginine vasopressin rose from a mean basal value of 0.4 +/- 0.2 (+/- SE) pmol/L to a maximum of 1.3 +/- 0.6 pmol/L, and plasma oxytocin rose from 0.7 +/- 0.1 pmol/L to a maximum of 1.2 +/- 0.2 pmol/L 30 min after the onset of hypoglycemia. The plasma arginine vasopressin and oxytocin concentrations after hypoglycemia were significantly higher in both of the diabetic groups compared with those in the normal group. Arginine vasopressin and oxytocin rose in all control subjects after hypoglycemia. The individual hormonal profiles in the diabetic patients were variable, with an exaggerated rise of oxytocin in some diabetic patients and no rise in others. The arginine vasopressin responses were exaggerated in all of the diabetic patients. There was no correlation between the hormonal responses and the duration of diabetes. The exaggerated plasma arginine vasopressin and oxytocin responses to hypoglycemia in diabetic patients may indicate the failure of a normal inhibitory mechanism which modulates hormonal secretion or a compensatory response to impaired glucose recovery.

Suppression of plasma intact parathyroid hormone levels during insulin-induced hypoglycemia in humans.

The adrenergic control of intact PTH secretion was investigated by measuring its plasma concentration during insulin-induced hypoglycemia in normal human subjects under control conditions (n = 12) and after alpha (n = 5)- or beta (n = 6)-adrenoceptor blockade. Blood samples were taken at baseline, at the time of the acute hypoglycemic reaction, and at regular intervals for 60 min thereafter. Plasma concentrations of intact PTH, catecholamines, total calcium, magnesium, albumin, phosphate, and glucose were measured in all subjects, and plasma ionized calcium was also assayed in three subjects during acute hypoglycemia without pharmacological blockade. At the time of the acute hypoglycemic reaction, the plasma concentration of intact PTH in the control subjects fell to 60.8% of baseline values and was accompanied by a small but significant increase in plasma total calcium. Intact PTH concentrations remained suppressed after the plasma calcium concentration had returned to normal. The two groups of subjects who were exposed to adrenoceptor blockade exhibited a reduced fall in plasma intact PTH and showed no significant increase in plasma total calcium. Therefore, insulin-induced acute hypoglycemia was associated with a fall in plasma intact PTH. Adrenoceptor blockade reduced, but did not abolish, the response, suggesting that other factors are involved.

The relationship between colonisation, secretor status and in-vitro adhesion of Candida albicans to buccal epithelial cells from diabetics.

This study investigated whether oral candida infection in diabetics and adhesion of Candida albicans to buccal epithelial cells in vitro were related. Buccal cells from 50 patients with diabetes mellitus showed a significant increase in adhesion of C. albicans strain CDS 88 compared with those collected from 50 non-diabetic controls matched for age, sex and denture status. Oral candida carriage, candida infection and secretor status were also investigated in both groups. The frequency of carriage was increased, but not significantly, and there was a significantly higher incidence of candida infection in diabetic patients compared with controls. Diabetic patients who were non-secretors had a significantly increased frequency of oral candida carriage.

Elevation of blood lactate and pyruvate levels in acute intermittent porphyria--a reflection of haem deficiency?

Blood lactate concentrations after glucose loading were significantly higher in 6 patients with acute intermittent porphyria in clinical remission than in 6 control subjects and the percentage rise in glucose pyruvate and lactate concentrations were greater in the porphyric subjects than in the control group. It is postulated that the raised lactate levels in the porphyric patient group may reflect haem deficiency affecting the cytochromes of the terminal respiratory chain.

Usefulness of cardiovascular tests of autonomic function in asymptomatic diabetic patients.

A group of five cardiovascular tests of autonomic neural function was studied in 115 asymptomatic insulin-dependent diabetic patients and nine patients with symptoms of diabetic autonomic neuropathy. In the asymptomatic group, 34 patients had one or more abnormal test. R-R variation during deep breathing was most frequently abnormal, but reliance on this test alone to examine parasympathetic function would have missed 12 of the 34 abnormal patients. The two abnormal responses to isometric exercise in this group were probably false-positive results caused by poor patient effort. In the symptomatic patients, R-R variation during deep breathing was abnormal in all nine, the blood pressure response to standing was abnormal in seven, and the response to isometric exercise was abnormal in three. The blood pressure response to isometric exercise is uncomfortable, requires special equipment, and should probably be confined to the assessment of symptomatic patients in a specialist setting.

Salivary secretion of albumin in type 1 (insulin-dependent) diabetes.

The concentration of albumin in saliva is low in healthy humans. To determine whether alterations in capillary permeability in diabetes affects the salivary glands, the concentration of albumin in parotid saliva was measured in 26 Type 1 (insulin-dependent) diabetic patients, and compared to 32 non-diabetic control subjects. The diabetic patients were subdivided into 3 groups on the basis of the urinary excretion of albumin in timed overnight collections of urine: (1) normal albumin excretion (less than 30 micrograms/min) n = 13; (2) microalbuminuria (30-300 micrograms/min) n = 7, and (3) macroalbuminuria (greater than 300 micrograms/min) n = 6. Saliva was collected for one minute following stimulation with 1 ml 10% citric acid, and the concentration of albumin was measured by a sensitive ELISA method. No significant difference in salivary albumin concentration was found between the control group and any of the diabetic groups. Thus, although urinary albumin excretion was increased, suggesting altered capillary permeability, simultaneous leakage of albumin into saliva was not observed. Measurement of salivary albumin concentration does not, therefore, provide a marker of occult microvascular disease in diabetes.

Attenuated neutrophil respiratory burst following acute hypoglycaemia in diabetic patients and normal subjects.

The effects of insulin-induced hypoglycaemia on the neutrophil respiratory burst were investigated in six patients with type 1 diabetes and six non-diabetic control subjects. Plasma glucose reached similar nadirs in control subjects (0.9 +/- 0.1 mmol 1(-1); mean +/- SEM) and diabetic patients (1.2 +/- 0.2 mmol 1(-1)) (NS). The resting neutrophil respiratory burst was similar in control subjects (1.26 +/- 0.15 mV) and diabetic patients (1.03 +/- 0.18 mV) (NS). The neutrophil respiratory burst fell following hypoglycaemia in control subjects and diabetic patients to 0.38 +/- 0.05 mV (P < 0.001) and 0.54 +/- 0.09 mV (P < 0.05), respectively. This fall was significantly greater in control subjects (ANOVA; P < 0.001). Resting neutrophil counts were not significantly different in control subjects (3.2 +/- 0.3 x 10(9) 1(-1)) and diabetic patients (6.1 +/- 1.5 x 10(9) 1(-1)). Following hypoglycaemia, neutrophil numbers increased in control subjects and diabetic patients to 11.5 +/- 1.4 x 10(9) 1(-1) (P < 0.01) and 9.7 +/- 1.7 x 10(9) 1(-1) (P < 0.05), respectively. This increase was significantly greater in control subjects (ANOVA; P < 0.001). These results suggest that the neutrophil respiratory burst is suppressed in response to hypoglycaemia and that this phenomenon is more pronounced in non-diabetic subjects.

Recreational overdosage of carbamazepine in Paisley drug abusers.

Oral drug abuse is a major social and medical issue. Paisley, in the West of Scotland, has become infamous for its problem with oral temazepam abuse. With the crack down on the prescription of temazepam in our area and the resultant lack of its supply on the streets, drug abusers appear to be experimenting with new drugs for their psychotropic effects. We report five cases of recreational carbamazepine overdosage in young temazepam abusers.

Metastatic pancreatic polypeptide producing tumour presenting with diabetes mellitus.

A metastatic pancreatic polypeptide tumour is described which presented clinically with diabetes mellitus. This is the first case to present this way.