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P J Weston

Publications and source records attributed to P J Weston.

At least 19 recordsLinked to original sources
PubMed2005

Non islet cell tumor hypoglycaemia in a metastatic Leydig cell tumor.

Non islet cell tumour hypoglycaemia (NICTH) is a rare cause of hypoglycaemia associated with malignancy and can be considered as a paraneoplastic syndrome. The hormonal factor associated with this condition is big IGF II, which exerts negative feedback effect and decreases the production of growth hormone and insulin. Due to low growth hormone levels, hepatic production of IGFBP 3 (the main binding protein of IGF II) is impaired. Excess free big IGF II is thus available for binding with insulin receptors to cause hypoglycaemia. Treatment options are either surgical removal of the tumour, administration of growth hormone, glucocorticoids or combination of treatments. A case of metastatic Leydig cell tumour causing NICTH has been discussed and the mechanism of NICTH hypoglycaemia and the treatment is outlined.

Aged↗
PubMed2005

Feasibility and safety of early transfer of premature infants from incubators to cots: a pilot study.

OBJECTIVES: To document whether medically stable infants can be transferred safely from incubators to unheated, open cots at 1500 g. METHODS: Four cohorts were recruited in a stepwise observational trial of transfer from incubators to unheated, open cots. We aimed to transfer the first 15 infants into cots on reaching a weight of 1800 g, the second at 1700 g, the third at 1600 g and the fourth at 1500 g. Nursery temperatures were set at 25 degrees C. The primary outcome measure was failure of transfer defined as the inability to maintain body temperatures in a cot despite additional coverings, with two consecutive axillary temperatures below 36.6 degrees C 1 h apart. Secondary aims were to determine temperature stability, growth, medical complications and time to discharge for these infants. Weight and corrected gestation at discharge were recorded. RESULTS: A total of 61 infants were recruited and transferred into cots. Cohorts were similar in gestation and sex. Infants recruited to the 1500 g cohort had higher birthweights than the other cohorts. There was no difference in the rate of infants failing transfer into cots between cohorts. Rate of weight gain before and after transfer and the number of high and low temperatures per infant after transfer was not different between cohorts. There were no differences between cohorts for discharge weight or corrected gestation. CONCLUSIONS: The results of this pilot study indicate the potential to transfer very low birthweight infants to an open unheated cot at a bodyweight of 1500 g. This study provides information for the design of future randomized controlled trials that are required to confirm the findings of this study before routine adoption of this intervention into clinical practice.

Body Temperature Regulation↗
PubMed2001

Beta blocker prescribing differences in patients with and without diabetes following a first myocardial infarction.

AIMS: To document the prescribed usage of beta blockers in patients with and without diabetes mellitus discharged from hospital following a first myocardial infarction. METHODS: All patients with diabetes and a group of patients matched for age and sex without diabetes, admitted with a documented first myocardial infarction during the period 1995-1999 at the Royal Liverpool University Hospital, Liverpool, UK were audited. RESULTS: Data were available on 201 patients with diabetes and 199 patients without diabetes. No significant differences existed between the diabetic and non-diabetic groups for age and sex. Twenty-three per cent of patients with diabetes were prescribed a beta blocker compared to 52% of non-diabetic patients (P < 0.01). Patients with diabetes had a higher frequency of perceived contraindications than patients without diabetes (36 vs. 27%, P < 0.001). Thirty-five per cent of patients with diabetes and 18% of non-diabetic patients had no contraindication to the use of beta blocker but were not prescribed one (P < 0.001). CONCLUSIONS: Although beta blockers can provide useful benefits in patients with diabetes following a myocardial infarction, this study suggests that a significant proportion of patients with diabetes and without a contraindication to treatment are still not receiving beta blockers after myocardial infarction.

Adrenergic beta-Antagonists↗
PubMed2000

The effect of selenium supplementation on outcome in very low birth weight infants: a randomized controlled trial. The New Zealand Neonatal Study Group.

BACKGROUND: Low selenium (SE) status has been documented in preterm infants and has been suggested to be a risk factor for chronic lung disease. METHODS: A total of 534 infants with birth weight <1500 g were enrolled in 8 New Zealand centers in a double-blind placebo-controlled randomized trial of SE supplementation from week 1 of life until 36 weeks' postmenstrual age or discharge home. Supplemented infants received 7 microg/kg/d of SE when fed parenterally and 5 microg/kg/d when fed orally. Plasma SE and glutathione peroxidase concentrations were measured in mothers after delivery and in infants before randomization and at 28 days and 36 weeks' postmenstrual age. Primary outcome measures were oxygen dependency at 28 days and total days oxygen dependency. RESULTS: No significant differences were seen between the groups with respect to primary or secondary outcome measures, with the exception that fewer supplemented infants had an episode of sepsis after the first week of life (P <.038). Mean plasma SE concentrations were 0.33 micromol/L before randomization in both groups and at 28 days had risen in the supplemented group (0.56 micromol/L) but fallen in the control group (0.29 micromol/L) (P <.0001). There was no association between outcome measures and SE concentrations at 28 days or 36 weeks' postmenstrual age. However, lower maternal and infant prerandomization SE concentrations were associated with increased respiratory morbidity. CONCLUSIONS: Postnatal SE supplementation in very low birth weight infants did not improve neonatal outcome. Further investigation of SE supplementation of mothers from the second half of pregnancy is warranted.

Double-Blind Method↗
PubMed1999

Is undetected autonomic dysfunction responsible for sudden death in Type 1 diabetes mellitus? The 'dead in bed' syndrome revisited.

AIMS: Sudden nocturnal death in young persons with Type 1 diabetes mellitus has been recently described, and is known as the 'dead in bed' syndrome. Its aetiology is unknown, and we have therefore explored the details of all papers recording the syndrome, to formulate a hypothesis of causation. METHODS: Literature review of 'dead in bed' reports as well as of nocturnal hypoglycaemia, and autonomic dysfunction in relation to baroreceptor-cardiac reflex sensitivity. RESULTS: Clinical reports of 'dead in bed' cases strongly suggest that nocturnal hypoglycaemia is a likely precipitant, but that the death is sudden and probably arrhythmic. Ventricular dysrhythmias may occur in the context of early autonomic neuropathy, with relative sympathetic overactivity, in young Type 1 diabetic persons. CONCLUSION: We conclude that the 'dead in bed' syndrome probably occurs in Type 1 diabetic persons with early autonomic neuropathy, resulting in relative sympathetic overactivity. In such persons, risks of ventricular dysrhythmias will be compounded by nocturnal hypoglycaemia, which may be associated with an increase in the electrocardiographic Q-T interval, and Q-T dispersion. This could lead to the observed sudden death in undisturbed beds. Further research in this area is urgently needed, in particular into the possible protective use of drugs that modulate the autonomic nervous system.

Autonomic Nervous System Diseases↗
PubMed1999

Older subjects show no age-related decrease in cardiac baroreceptor sensitivity.

OBJECTIVE: To examine the relationship between age, blood pressure and cardiac baroreceptor sensitivity derived from spectral analysis, the Valsalva manoeuvre and impulse response function. METHODS: We studied 70 healthy normotensive volunteers who were free from disease and not taking medication with cardiovascular or autonomic effects. We measured beat-to-beat arterial blood pressure and used standard surface electrocardiography to record pulse interval under standardized conditions with subjects resting supine as well as during three Valsalva manoeuvres. We performed single, multiple and stepwise regression of patient characteristics against cardiac baroreceptor sensitivity results. RESULTS: There is a non-linear decline in cardiac baroreceptor sensitivity with advancing age, increasing systolic blood pressure and heart rate values (except for the Valsalva-derived result), but little further decline after the fourth decade. Only age significantly influenced values derived using the Valsalva manoeuvre and impulse response analysis. Using spectral analysis, age, systolic and diastolic blood pressure and heart rate influenced cardiac baroreceptor sensitivity, age contributing to 50% of the variability. Age also influenced the relationship between pulse interval and blood pressure, possibly indicating more non-baroreceptor-mediated changes with advancing age. CONCLUSIONS: Although age is the dominant factor influencing cardiac baroreceptor sensitivity in this normotensive population, there is little change in mean values after 40 years of age. The differences in the relationship between pulse interval and blood pressure with advancing age have implications for the calculation of cardiac baroreceptor sensitivity using spectral analysis.

Adult↗
PubMed1998

An automatic device for the assessment of cardiovascular autonomic function.

Autonomic neuropathy is a common complication of diabetes mellitus and is associated with significant morbidity and possibly an increase in mortality. Despite this, however, autonomic dysfunction is not usually sought in the routine assessment of diabetic patients. We report the development and testing of a small, portable and reliable device that allows the routine testing of cardiac autonomic function in the outpatient setting with minimal inconvenience to the patient. This should facilitate the accurate assessment both of patients with symptoms suggestive of autonomic dysfunction and of autonomic function in research.

Arrhythmias, Cardiac↗
PubMed1998

Evidence of defective cardiovascular regulation in insulin-dependent diabetic patients without clinical autonomic dysfunction.

(1) Autonomic dysfunction is a well recognised complication of diabetes mellitus and early detection may allow therapeutic manoeuvres to reduce the associated mortality and morbidity. We sought to identify early cardiovascular autonomic neuropathy using spectral analysis of heart rate and systolic blood pressure variability. (2) Thirty patients with Type 1 (insulin-dependent) diabetes mellitus (DM) and 30 matched control subjects were studied. In addition to standard tests of autonomic function, heart rate and systolic blood pressure variability were assessed using power spectral analysis. From the frequency domain analysis of systolic blood pressure and R-R interval, the overall gain of baroreflex mechanisms was assessed. (3) Standard tests of autonomic function were normal in both groups. Total spectral power of R-R interval was reduced in the Type 1 DM group for low-frequency (473 +/- 63 vs. 747 +/- 78 ms2, mean +/- S.E.M., P = 0.002) and high-frequency bands (125 +/- 13 vs. 459+/-90 ms2, P < 0.0001). Systolic blood pressure low-frequency power was increased in the diabetic group (9.3 +/- 1.2 vs. 6.6+/-0.7 mmHg2, P < 0.05). The low frequency/high frequency ratio for heart rate variability was significantly higher in the Type 1 DM patients (4.6+/-0.5 vs. 2.9+/-0.5, P = 0.002), implying a relative sympathetic predominance. When absolute powers were expressed in normalised units, these differences persisted. There were significant reductions in baroreceptor-cardiac reflex sensitivity in Type 1 DM patients compared to controls while supine (9.7+/-0.7 vs. 18.5 +/- 1.7 ms/mmHg, P < 0.0001) and standing (2.9+/-0.9 vs. 7.18+/-1.9 ms/mmHg, P < 0.001). (4) Spectral analysis of cardiovascular variability detects autonomic dysfunction more frequently in Type 1 DM patients than conventional tests, and is suggestive of an abnormality of parasympathetic function. The abnormality of baroreceptor-cardiac reflex sensitivity could be explained by this impairment of parasympathetic function and this may predispose to the development of hypertension and increase the risk of sudden cardiac death. Using spectral analysis methods may allow detection of early diabetic cardiac autonomic neuropathy and allow therapeutic intervention to slow the progression.

Adult↗
PubMed1997

Is impaired baroreflex sensitivity a predictor or cause of sudden death in insulin-dependent diabetes mellitus?

Sudden death at night is known to occur in young patients with insulin-dependent (Type 1) diabetes mellitus (IDDM) but the aetiology is uncertain. A cardiac arrhythmia has been postulated, but there has been little evidence to support this. We present the case of a 31-year-old man with IDDM of 17 years duration, who died suddenly while asleep. Over preceding months, he had had strict glycaemic control (HbA1 8.9%), normal 24 h blood pressure (mean 131 +/- 2.1/76 +/- 2.2 mmHg), no evidence of microangiopathy or endothelial dysfunction and normal standard clinical tests of autonomic function. An electrocardiogram was similarly unremarkable, with a QTc interval of 0.414 s, and an echocardiogram had demonstrated normal left ventricular mass index (96.4 g m-2). However, there was no nocturnal dip in heart rate (daytime 74 +/- 2.7, and nocturnal 68 +/- 1.6 beats min-1), and he had grossly impaired baroreflex sensitivity during Phase 4 of the valsalva manoeuvre (0.5 ms mmHg-1), with power spectral analysis studies suggesting an abnormality of parasympathetic function. The coroner's autopsy demonstrated no structural abnormalities. We hypothesize that abnormal baroreflex sensitivity could either predict a risk of or account for some of the unexplained deaths in IDDM, in that relative overactivity of the sympathetic nervous system could cause ventricular arrhythmias.

Adult↗
PubMed1997

Randomised trial of dopamine compared with hydrocortisone for the treatment of hypotensive very low birthweight infants.

AIM: To compare the efficacy of hydrocortisone with dopamine for the treatment of hypotensive, very low birthweight (VLBW) infants. METHODS: Forty infants were randomly allocated to receive either hydrocortisone (n = 21) or dopamine (n = 19). RESULTS: All 19 infants randomised to dopamine responded; 17 of 21 (81%) did so in the hydrocortisone group. Three of the four non-responders in the hydrocortisone group had clinically significant left to right ductal shunting. The incidence of bronchopulmonary dysplasia, retinopathy of prematurity, intraventricular haemorrhage, necrotising enterocolitis, symptomatic patent ductus arteriosus, hyperglycaemia, sepsis (bacterial or fungal) or survival did not differ between groups. The adrenocorticotrophic hormone (ACTH) stimulated plasma cortisol activity, either before or after treatment, did not differ between the two groups of infants. Although a significant difference in efficacy between dopamine and hydrocortisone was not noted (P = 0.108), there were four treatment failures in the hydrocortisone group, compared with none in the dopamine group. CONCLUSION: Both hydrocortisone and dopamine are effective treatments for hypotension in very low birthweight infants.

Anti-Inflammatory Agents↗
PubMed1997

Can abnormalities of ventricular repolarisation identify insulin dependent diabetic patients at risk of sudden cardiac death?

OBJECTIVE: To study the possible association or QT dispersion and mean QTc intervals, as measured from standard 12 lead electrocardiograms, with baroreceptor-cardiac reflex sensitivity (BRS) in insulin dependent diabetic patients. DESIGN: Comparative study of non-invasive assessment of BRS, QT interval, and QT dispersion. SETTING: Large teaching hospital. SUBJECTS: 31 young asymptomatic, normotensive, insulin dependent diabetic patients, aged 20-55 years with normal clinical autonomic function. METHODS: QT intervals and QT dispersion were measured by a single observer blinded to other data about the patients. BRS was measured after activating the baroreflex with a Valsalva manoeuvre, and the rate in change of R-R interval to increasing systolic pressure during phase 4 was measured; in addition sequence analysis of resting systolic blood pressure and heart rate was performed during standing. The alpha coefficient--an index of the overall gain of the baroreflex mechanisms--was estimated from spectral analysis data of systolic blood pressure and pulse interval variability. RESULTS: Mean (SD) QTc interval was 406 (23) ms, QT dispersion was 44 (13) ms. There was no association between QT dispersion and any measurement of BRS. There was a negative correlation between mean QTc intervals and sequence analysis BRS (r = -0.355, P = 0.049), but no association with Valsalva BRS. The alpha coefficient, showed a significant negative correlation with mean QTc (r = -0.42, P = 0.008). CONCLUSIONS: Abnormal BRS may be reflected in the heart by global prolongation of ventricular repolarisation, but not by dispersion of ventricular repolarisation. This may, in part, explain the increase in sudden cardiac death seen in IDDM patients.

Adult↗
PubMed1996

Assessment of baroreceptor-cardiac reflex sensitivity using time domain analysis in patients with IDDM and the relation to left ventricular mass index.

Autonomic dysfunction in insulin-dependent diabetic (IDDM) patients has been associated with abnormalities of left ventricular function and an increased risk of sudden death. A group of 30 patients with IDDM and 30 age, sex and blood pressure matched control subjects underwent traditional tests of autonomic function. In addition, baroreceptor-cardiac reflex sensitivity (BRS) was assessed using time domain (sequence) analysis of systolic blood pressure and pulse interval data recorded non-invasively using the Finapres beat-to-beat blood pressure recording system. 'Up BRS' sequences-increases in systolic blood pressure associated with lengthening of R-R interval, and 'down BRS' sequences-decreases in systolic blood pressure associated with shortening of R-R interval were identified and BRS calculated from the regression of systolic blood pressure on R-R interval for all sequences. We also assessed heart rate variability using power spectral analysis and, after expressing components of the spectrum in normalised units, assessed sympathovagal balance from the ratio of low to high frequency powers. IDDM subjects underwent 2-D echocardiography to assess left ventricular mass index. Standard tests of autonomic function revealed no differences between IDDM patients and control subjects, but dramatic reductions in baroreceptor-cardiac reflex sensitivity were detected in IDDM patients. 'Up BRS' when supine was 11.2 +/- 1.5 ms/mmHg (mean +/- SEM) compared with 20.4 +/- 1.95 in control subjects (p < 0.003) and when standing was 4.1 +/- 1.9 vs 7.6 +/- 2.7 ms/mmHg (p < 0.001). Down BRS when supine was 11.5 +/- 1.2 vs 22 +/- 2.6 (p < 0.001) and standing was 4.4 +/- 1.9 vs 7.3 +/- 2.5 ms/mmHg (p < 0.003). There were significant relations between impairment of the baroreflex and duration of diabetes (p < 0.001) and poor glycaemic control (p < 0.001). From a fast Fourier transformation of supine heart rate data and using a band width of 0.05-0.15 Hz as low-frequency and 0.2-0.35 Hz as high frequency total spectral power of R-R interval variability was significantly reduced in the IDDM group for both low-frequency (473 +/- 62.8 vs 746.6 +/- 77.6 ms2 p = 0.002) and high frequency bands 125.2 +/- 12.9 vs 459.3 +/- 89.8 ms2 p < 0.0001. When the absolute powers were expressed in normalised units the ratio of low frequency to high frequency power (a measure of sympathovagal balance) was significantly increased in the IDDM group (2.9 +/- 0.53 vs 4.6 +/- 0.55, p < 0.002 supine: 3.8 +/- 0.49 vs 6.6 +/- 0.55, p < 0.001 standing). Thus, time domain analysis of baroreceptor-cardiac reflex sensitivity detects autonomic dysfunction more frequently in IDDM patients than conventional tests. Impaired BRS is associated with an increased left ventricular mass index and this abnormality may have a role in the increased incidence of sudden death seen in young IDDM patients.

Adult↗
PubMed1996

Abnormal baroreceptor-cardiac reflex sensitivity is not detected by conventional tests of autonomic function in patients with insulin-dependent diabetes mellitus.

1. Autonomic neuropathy is a common complication of diabetes mellitus and is a major risk factor for sudden death. 2. A group of 30 patients with insulin-dependent diabetes mellitus and 30 age-, sex- and blood pressure-matched control subjects underwent traditional tests of autonomic function. Resting supine R-R interval and systolic blood pressure variability were assessed using spectral analysis methods. In addition, we assessed the baroreceptor-cardiac reflex from the linear relation of the change in R-R interval to the increasing systolic blood pressure measured non-invasively with the Finapres monitor during phase 4 of the Valsalva manoeuvre and from resting heart rate and systolic blood pressure power spectra. 3. Whereas standard tests of autonomic function revealed no differences between patients with insulin-dependent diabetes mellitus and control subjects, there was a significant reduction in power spectral density of heart rate variability around the high-frequency region (125.2 +/- 112.9 versus 459.3 +/- 189.8 ms2, mean +/- SD). Furthermore, reductions in baroreflex sensitivity calculated from the Valsalva manoeuvre were detected in diabetics compared with controls (3.3 +/- 1.6 versus 9.5 +/- 2.5 ms/mmHg, mean +/- SD, P < 0.00001). There were significant relations between impairment of the baroreflex and duration of diabetes (P < 0.001) and poor diabetic control (P < 0.05). 4. In summary, autonomic dysfunction occurs much more frequently in diabetic patients than conventional tests would suggest. Abnormal baroreceptor-cardiac reflex sensitivity in patients with insulin-dependent diabetes mellitus may in part be explained by abnormal parasympathetic function. This unrecognized abnormality may have a role in the increased incidence of sudden death seen in young diabetic subjects.

Adult↗
PubMed1996

Reproducibility and automatic measurement of QT dispersion.

This study investigated interobserver (two observers) and intrasubject (two measurements) reproducibility of QT dispersion from abnormal electrocardiograms in patients with previous myocardial infarction, and compared a user-interactive with an automatic measurement system. Standard 12-lead electrocardiograms, recorded at 25 mm.s-1, were randomly chosen from 70 patients following myocardial infarction. These were scanned into a personal computer, and specially designed software skeletonized and joined each image. The images were then available for user-interactive (mouse and computer screen), or automatic measurements using a specially designed algorithm. For all methods reproducibility of the RR interval was excellent (mean absolute errors 3-4 ms, relative errors 0.3-0.5%). Reproducibility of the mean QT interval was good; intrasubject error was 6 ms (relative error 1.4%), interobserver error was 7 ms (1.8%), and observers' vs automatic measurement errors were 10 and 11 ms (2.5, 2.8%). However QTc dispersion measurements had large errors for all methods; intrasubject error was 12 ms (17.3%), interobserver error was 15 ms (22.1%), and observers' vs automatic measurement were errors 30 and 28 ms (35.4, 31.9%). QT dispersion measurements rely on the most difficult to measure QT intervals, resulting in a problem of reproducibility. Any automatic system must not only recognize common T wave morphologies, but also these more difficult T waves, if it is to be useful for measuring QT dispersion. The poor reproducibility of QT dispersion limits its role as a useful clinical tool, particularly as a predictor of events.

Diagnosis, Computer-Assisted↗