Insulin sensitivity after phototherapy for seasonal affective disorder.
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Diabetes Mellitus, Type 1↗
Biomedical subjects
D Kerr
Publications and source records attributed to D Kerr.
The quality and relevance of peripheral neuropathy data on a diabetic clinical information system.
Routinely collected peripheral neuropathy data entered on a diabetic clinical information system since 1979 have been audited for completeness, consistency, accuracy (inter-observer variation), validity by comparison with biothesiometry, and relevance by life table analysis for foot ulceration. Peripheral neuropathy was defined by a neuropathy disability score > or = 4. The data were 98% complete. Forty-nine of 3405 (1.4%) had inconsistent records. Agreement between observers for clinical examination was significant (p < 0.05) for aggregate neuropathy score and its individual components except the knee jerk: Kappa score for observer variation for neuropathy score 0.56 (95% confidence interval 0.36-0.76). There was good agreement between neuropathy defined as aggregate score > or = 4, and as combined vibration perception thresholds for both feet > 60 V: Kappa statistic 0.62 (95% confidence interval 0.44-0.80). The chance of developing a foot problem in 3 years increased from 3% for patients with a score of zero to 45% for people with a score of between 9 and 12. We conclude that the calculation of a clinical neuropathy score is a simple, valid and relevant method for diabetes care both in hospital and the community. When combined with palpation of peripheral pulses most patients at risk of foot ulceration can be identified allowing targeting of preventive chiropody and orthotic resources.
Diabetic Neuropathies↗
Ondansetron compared with metoclopramide in the control of emesis and quality of life during repeated chemotherapy for breast cancer.
This was a multicentre, randomised, double-blind, parallel-group study which included female breast cancer patients, receiving their first of 6 scheduled courses of chemotherapy (cyclophosphamide greater than or equal to 500 mg/m2). Patients received an intravenous dose of 16 mg dexamethasone with either 8 mg ondansetron or 60 mg metoclopramide before chemotherapy, followed by oral dosing with 8 mg ondansetron or 20 mg metoclopramide 3 times daily for 5 days. A total of 93 patients were treated with ondansetron and 94 patients with metoclopramide. On day 1 of their first course of treatment 91 and 60% of patients in the ondansetron and metoclopramide groups respectively were free of emesis (p less than 0.001). Over the 5-day treatment period, the corresponding figures were 81 and 48% (p less than 0.001). The results for nausea also revealed highly statistically significant treatment differences (p less than 0.001) in favour of ondansetron for both day 1 and day 1-5 analyses of the first treatment course. Over the series of courses, 67% of patients receiving ondansetron completed all 6 courses with a maximum of 2 emetic episodes on their worst day, compared with 28% of patients receiving metoclopramide (p less than 0.001). A similar analysis for nausea revealed that 49% of patients receiving ondansetron completed all 6 courses with 'none' or 'mild' nausea compared with 27% of patients receiving metoclopramide (p less than 0.001). These differences were reflected in quality of life data (Rotterdam Symptom Checklist). After the first course of treatment, a statistically significant improvement (p = 0.002) in the psychological subscale scores was observed after ondansetron compared with metoclopramide. No differences were observed in the physical or functional activity subscales after the first course. However, the quality of life results over the series of courses revealed a more pronounced difference in favour of ondansetron in the psychological subscale scores (p less than 0.001) as well as trends in favour of ondansetron in the physical (p = 0.096) and functional activity (p = 0.056) subscales. Extrapyramidal symptoms were reported in 19% of patients in the metoclopramide group and resulted in 15% of patients withdrawing from their randomised anti-emetic schedule, either during or between treatment courses. Other adverse events were generally minor in nature and did not necessitate withdrawal from treatment. In conclusion, this study shows that ondansetron is significantly superior to metoclopramide (each with a single pre-treatment dose of dexamethasone) in the control of emesis over 6 courses of chemotherapy for breast cancer.(ABSTRACT TRUNCATED AT 400 WORDS)
Adult↗
A recombinant cDNA derived from human brain encodes a DNA binding protein that stimulates transcription of the human neurotropic virus JCV.
The human neurotropic virus JCV contains a 98-base pair repeat enhancer/promoter sequence that confers glial-specific transcription to the viral early and late promoters. The central region of this repeat, designated the B-domain, binds to a glial-derived nuclear protein that stimulates transcription of the viral promotor in vitro. We now report the isolation of a recombinant cDNA clone, termed glial factor-1 (GF1), from a brain expression library that encodes a novel protein which interacts with the JCV B-domain. Results from RNA studies indicate that the GF1 transcript is more abundant in brain than in other tissues and that the level of GF1 RNAs increases progressively during brain development. Cotransfection of the recombinant GF1 expressor plasmid with JCV promoters indicates that GF1 stimulates transcription of the JCV late promoter and to a lesser extent the JCV early promoter predominantly in cells of human glial origin. Thus, GF1 is a sequence-specific DNA binding protein that may play a role in determining the glial-specific expression of JCV.
Amino Acid Sequence↗
Course of brittle diabetes: 12 year follow up.
OBJECTIVE: To determine the course of brittle diabetes. DESIGN: 12 year follow up of patients identified in 1977-9 as having brittle diabetes; retrospective review of the case notes. SETTING: Nottingham health district. SUBJECTS: 25 brittle diabetic patients were identified in 1979-9; 11 (five men) had three or more admissions with ketoacidosis between June 1977 and 1979 and 14 (eight men) had three or more attendances at the accident and emergency department with hypoglycaemia in 1978. Two controls from our diabetic register were matched to each patient for age, sex, and duration of diabetes. MAIN OUTCOME MEASURES: Frequency of ketoacidosis and severe hypoglycaemia in the 12 years after ascertainment; diabetic control and complications in 1988-90; retrospective attribution of the cause of brittleness. RESULTS: Patients with recurrent ketoacidosis had had a median (range) of 28 (8-67) episodes. One man died of a cerebral tumour but five of the surviving nine patients had not been admitted in the past two years, although diabetic control remained poor (median haemoglobin A1 concentration 14%). Seven patients had pure hypoglycaemic brittleness, and five had also had eight or more admissions with ketoacidosis (mixed brittleness). Two died of uraemia within a year after ascertainment and two others in hypoglycaemic coma seven and 12 years later. Brittle diabetes was in most cases related to a specific situation, usually unhappiness at home or school. CONCLUSIONS: Brittle diabetes is often episodic and almost always related to stressful life circumstances. Once the underlying cause is removed it tends to improve. Recurrent hypoglycaemic brittleness of psychological origin has a poor prognosis.
Adolescent↗
The examination of the nine month old infant.
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Age Factors↗
Flexible sigmoidoscopy may be ineffective for secondary prevention of colorectal cancer in asymptomatic, average-risk men.
Asymptomatic men (N = 114) 50 years of age or older had screening for colorectal neoplasia with flexible sigmoidoscopy followed by colonoscopy regardless of the sigmoidoscopic result. Our study objective was to determine the prevalence of patients having isolated adenomatous polyps in a proximal colonic segment in the absence of a distal index neoplasm within reach of the sigmoidoscope. Through the combined use of sigmoidoscopy and colonoscopy, adenomatous polyps were detected in 47 of 114 individuals (41%). A total of 88 adenomas was found. Seventeen patients had isolated neoplasms in proximal colonic segments in the absence of distal adenomas. These patients represented 15% of screened subjects (17 of 114) and 20% of individuals who lacked adenomas on sigmoidoscopy (17 of 84). The majority of proximal neoplasms were small (less than 1.0 cm), tubular adenomas. Flexible sigmoidoscopy may be ineffective for screening asymptomatic men for neoplasia. However, it remains to be determined if a 20% miss rate (for those with a normal sigmoidoscopic examination) is significant and whether small proximal adenomas are worth finding.
Adenoma↗
Importance of insulin in subjective, cognitive, and hormonal responses to hypoglycemia in patients with IDDM.
Not all episodes of hypoglycemia are recognized as such by diabetic patients, suggesting that it is possible for them to adapt to a low blood glucose level, although the mechanism involved is not known. The aim of this study was to examine whether insulin has an effect, independent of blood glucose, on the subjective, cognitive, and hormonal responses to hypoglycemia. Nine patients with insulin-dependent diabetes mellitus (IDDM) participated in three hyperinsulinemic glucose-clamp studies. After 60 min at 4.5 mM, blood glucose was randomized to be 1) maintained at 4.5 mM for 240 min, 2) lowered to 2.8 mM for 180 min followed by 60 min at 2 mM with an insulin infusion rate of 40 mU.m-2.m-1, and 3) fitted to the same protocol as 2 but with an infusion rate of 120 mU.m-2.min-1. Symptoms and awareness of hypoglycemia (100-mm visual analogue scales), cognitive function, and counterregulatory hormone levels were assessed every 30 min. There were no subjective or cognitive changes during the euglycemic study. Awareness and hypoglycemic symptoms (hunger, facial flushing, trembling, and sweating) were attenuated by the higher insulin infusion rate (P less than 0.05 and P less than 0.01, respectively). Cognition was significantly impaired after 60 min at 2.8 mM (P less than 0.001) and deteriorated further when the blood glucose level was lowered to 2 mM (P less than 0.01). Levels of cortisol (P less than 0.01) and growth hormone (P less than 0.05) but not epinephrine were suppressed by the higher insulin infusion rate.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
A nuclear protein derived from brain cells stimulates transcription of the human neurotropic virus promoter, JCVE, in vitro.
The 98-base pair enhancer/promoter sequence is critical for cell type-specific transcription of the human neurotropic viral promoter, JCVE, in glial cells. Transcriptionally active extracts were prepared from glial cells and used to identify cis- and trans-acting regulatory elements that are involved in the glial-specific activation of the JCVE promoter. Results indicate that multiple regulatory sequences within the 98-base pair repeat specifically bind to nuclear proteins present in glial cells and positively regulate viral early RNA synthesis. The central region of the repeat, designated domain-B, interacts with a 45-kDa nuclear protein present in brain cells. This brain-specific protein was purified by conventional and DNA affinity chromatography. Complementation of the highly purified protein with HeLa extract significantly increased JCVE promoter activity. Thus, association of the novel glial-origin transcription factor with its target sequence increases transcription of the JCVE promoter in a non-glial context.
Animals↗
Beta-adrenoceptor blockade and CNS-related subjective symptoms: a randomized, double-blind, placebo-controlled comparison of metoprolol CR/ZOK, atenolol and propranolol LA in healthy subjects.
The effect of once daily treatment with atenolol (100 mg), metoprolol CR/ZOK (100 mg) and propranolol LA (160 mg) for one week on CNS-related subjective symptoms was compared with that of placebo using a randomised, double-blind cross-over design in 12 healthy volunteers. The symptoms were recorded using a previously documented self-administered questionnaire (MSE-profile), which included three dimensions: Contentment, Vitality and Sleep. Compared to placebo, all three beta-adrenoceptor antagonists reduced the exercise heart rate at 24 hours but a somewhat more pronounced effect was found with propranolol LA. No significant difference in any of the dimensions was detected between placebo and either metoprolol CR/ZOK or atenolol tablets. Following propranolol LA treatment a deterioration in the dimensions Vitality and Sleep was observed compared with both placebo and the beta 1-selective drugs. Difference in lipophilicity between the beta 1-selective agents metoprolol and atenolol has little bearing on the occurrence of the CNS-related symptoms, in comparison to the marked effects of the lipophilic and nonselective compound propranolol.
Adrenergic beta-Antagonists↗
Treatment of Paget's disease with intermittent low-dose infusions of disodium pamidronate (APD).
Disodium pamidronate (APD) is a potent inhibitor of bone resorption, with less risk of defective mineralization than earlier bisphosphonates. We assessed the response to six spaced low-dose intravenous infusions of APD given at intervals of approximately 6 weeks followed by weekly infusions if bone turnover remained abnormal. Three groups of 10 patients were studied, each group receiving infusions of 15, 30, or 45 mg. Hydroxyproline excretion fell by 62% and alkaline phosphatase was reduced by 72%, with no difference between the dose levels. A total of 21 patients (70%) achieved normal levels of bone turnover, indicating that low-dose infusions of APD are a safe and effective treatment for Paget's disease.
Alkaline Phosphatase↗
Alcohol causes hypoglycaemic unawareness in healthy volunteers and patients with type 1 (insulin-dependent) diabetes.
Both hypoglycaemia and alcohol consumption affect cognitive function but it is unclear whether moderate drinking alters awareness of hypoglycaemia. We have examined this in a single blind randomised hyperinsulinaemic clamp study in eight non-diabetic subjects and seven Type 1 (insulin-dependent) diabetic patients. After 30 min of euglycaemia (blood glucose 4.5 mmol/l) subjects drank either 0.75 g/kg ethanol or a placebo drink after which blood glucose was lowered to 2.5 mmol/l for 40 min. Awareness of hypoglycaemia, reaction time and physiological responses were measured before and after ethanol. At a blood glucose concentration of 4.5 mmol/l, ethanol (producing peak blood levels of 20-25 mmol/l) caused a transient increase in systolic blood pressure (p less than 0.05), a sustained increase in heart rate (p less than 0.01) and a slowing of reaction time in both normal subjects and diabetic patients. During hypoglycaemia in both groups, the slowing of reaction time and increase in sweating were more marked after ethanol than placebo (both p less than 0.05), while the increase in finger tremor (p less than 0.05) was blunted after ethanol, in both groups. Counter regulatory hormone secretion was not affected by ethanol. Despite increases in symptoms during hypoglycaemia, only 2 of 15 individuals "felt hypoglycaemic" after ethanol compared to 11 out of 15 after placebo. We conclude that after moderate drinking non-diabetic subjects and Type 1 diabetic patients are less aware of hypoglycaemia despite exaggerated physiological changes.
Adult↗
Gene expression in oestrogen-dependent human breast cancer xenograft tumours.
Xenograft tumours from an oestrogen-dependent human breast cancer cell line MCF-7 have been established and characterised in thymectomised, irradiated female CBA strain mice. There was evidence for selection in xenografts of a subpopulation of MCF-7 cells with an altered pattern of gene expression as measured by mRNA levels compared with the original cells in vitro. Tumorigenicity increased significantly on repeated animal passage but oestrogen dependence was retained. Following injection of the mice with oestrogen, mitosis was induced in the tumour cells with associated increases in thymidine uptake and percentage of cells in S-phase. In accord with these changes, c-myc and p53 expression were increased and TGF-beta was suppressed. Thereafter the expression of the c-myc and p53 genes fell whilst that of the TGF-beta gene was induced as the oestrogenic-stimulus declined. The oestrogen-regulated mRNA pS2 showed a biphasic response to oestrogen and levels declined as the serum oestrogen fell to undetectable levels. This xenograft system demonstrates that changes in transcription of oncogenes, growth factor and oestrogen-regulated genes can be detected in vivo in response to oestrogen. It thus provides an in vivo model for studies of the biochemical and molecular basis for therapeutic manipulation of hormone-sensitive human breast cancer.
Animals↗
Beta-adrenoceptor blockade and hypoglycaemia. A randomised, double-blind, placebo controlled comparison of metoprolol CR, atenolol and propranolol LA in normal subjects.
1. The effect of 1 week of treatment with propranolol LA (160 mg), atenolol (100 mg) and metoprolol CR (100 mg) on awareness of and the physiological responses to moderate hypoglycaemia were compared with placebo using a randomised, cross-over design in 12 healthy volunteers. 2. All three beta-adrenoceptor antagonists reduced resting heart rate, systolic blood pressure and heart rate responses to submaximal exercise compared with placebo. 3. Under hyperinsulinaemic (60 mu m-2 min-1) clamp conditions, at a blood glucose of 2.5 mmol l-1, atenolol prevented the rise in systolic and atenolol and metoprolol CR prevented the fall in diastolic blood pressure usually associated with hypoglycaemia. At this level of hypoglycaemia, the expected increase in heart rate was inhibited by atenolol but not metoprolol CR. Pre-treatment with propranolol LA resulted in a significant pressor response and a bradycardia during hypoglycaemia. In addition the normal increase in finger tremor was abolished by propranolol LA. 4. During hypoglycaemia all three beta-adrenoceptor blockers augmented sweating compared with placebo but hypoglycaemic symptoms, awareness and slowing of reaction time were the same with drugs and placebo. 5. The rise in plasma adrenaline and other counter-regulatory hormones during hypoglycaemia was enhanced by beta-adrenoceptor blockade. 6. We conclude that beta-adrenoceptor antagonists modify the physiological and hormonal responses to, but do not adversely affect awareness of, moderate hypoglycaemia in healthy volunteers.
Adrenergic beta-Antagonists↗
Steroid hormones and growth factors in breast cancer.
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Breast Neoplasms↗
Rapid diagnosis of lung cancer from palpable metastases by needle thrust.
This study encourages the use of percutaneous FNB to diagnose and stage advanced lung cancer in patients with palpable metastases in supraclavicular lymph nodes or soft tissues. Percutaneous FNB of metastases is much easier to learn than transthoracic needle aspiration: the superficial target is anchored and sampled with multiple passes using a short needle grasped directly in the fingers. It is fast, accurate, economical and nearly free of risk and pain. The technique saves time and money because it is the only procedure needed by many patients with palpable disease in stage IIIB and IV. Bronchoscopy, transthoracic needle aspiration and open surgical biopsy thus can be avoided in most patients with palpable metastases. Prompt diagnosis by FNB of metastases speeds palliation for patients with urgent need. Tumor cell type from FNB correlated with cytologic findings from sputum samples, bronchoscopy specimens and autopsy results.
Adult↗
Maintenance of serum calcium after total thyroparathyroidectomy.
We have studied calcium regulation in 11 consecutive patients undergoing radical surgery for upper aerodigestive tract malignancy. Eight patients received postoperative parenteral nutrition including calcium (19 mmol/day) and tri-iodothyronine (30 micrograms/day) supplementation. Three patients received enteral nutrition with calcium (70 mmol/day), 1.25 dihydroxycholecalciferol (1 microgram) and thyroxine (150 micrograms/day) via a nasogastric tube. Mean (SEM) corrected calcium fell from 2.42 (0.013) to 2.03 (0.036) mmol/l after 24 h (P less than 0.01). Replacement therapy generally maintained the serum calcium above 2.0 mmol/l. However, values were associated with only one episode of tetany. Phosphate increased from 1.10 (0.05) to 1.79 (0.11) mmol/l, 7-9 days postoperatively (P less than 0.001). Tubular calcium reabsorption fell and urinary calcium excretion rose, consistent with loss of parathyroid hormone (PTH) action on the distal nephron. However, the renal leak of calcium can be considerably reduced by concomitant salt depletion. This enhances proximal tubular sodium and calcium reabsorption thereby limiting calcium delivery to the distal nephron. This offsets the consequences of the loss of PTH which normally regulates distal calcium reabsorption.
Absorption↗
Adrenaline response to hypoglycaemia and insulin species.
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Adult↗