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Biomedical subjects

M D Peake

Publications and source records attributed to M D Peake.

At least 37 records · Page 2Linked to original sources
PubMed1989

Neuron-specific enolase can be used as the sole guide to treat small-cell lung cancer patients in common clinical practice.

Serum samples were collected from 115 small-cell lung cancer patients before each course of chemotherapy and during follow-up. Levels of neuron-specific enolase (NSE) were measured and compared to the clinical assessments of the course of the disease, which were done by the responsible physician without knowledge of NSE-values. The predictive accuracy of an increase or decrease of NSE for a major response (CR + PR), SD or PD was 98%. Importantly no false-positive rises of NSE were observed. On the basis of this large number of data it seems justified to conclude that in common clinical practice the treatment of small-cell lung cancer patients can be monitored by serial measurements of NSE alone.

Biomarkers, Tumor↗
PubMed1989

Bayesian derived predictions for twice daily theophylline under outpatient conditions and an assessment of optimal sampling times.

1. The accuracy of a computerised method of pharmacokinetic interpretation of a single serum theophylline concentration, employing the statistical technique of Bayesian analysis, has been evaluated for an oral slow release form of theophylline using twice daily dosing. 2. Twenty-four hour steady state serum theophylline concentration-time profiles of one Uniphyllin Continus 400 mg tablet (Napp Laboratories) every 12 h were measured in 15 patients. These profiles demonstrated a diurnal variation of theophylline absorption which was faster during the day. 3. Revised predictions of the profiles were generated by Bayesian analysis using a single serum theophylline concentration taken during a previous outpatient appointment. Comparing the predicted and measured profiles, the accuracy of the Bayesian method is considered more than adequate for clinical purposes. 4. The predictions produced by the revised estimates were statistically less biased and more precise than those derived by a theophylline algorithm using population data. 5. The mean prediction errors of the revised estimates of the day and night-peak drug concentrations were -0.55 mg l-1 and -0.21 mg l-1 whilst those of the evening and morning troughs were 1.17 mg l-1 and 0.41 mg l-1, respectively. 6. Analysis of the predictive and relative performance of the samples drawn during the profile revealed that the sample taken prior to a morning dose produced the most accurate predictions. 7. There was no statistical difference in the relative predictive performance of samples drawn up to 4 h before or 2 h after the morning dose. It is, therefore, recommended that all serum theophylline concentrations to be used in Bayesian analysis, should be drawn within this period.

Administration, Oral↗
PubMed1989

Familial malignant retroperitoneal paraganglioma.

Paragangliomas are neuroendocrine tumours and those occurring in the head and neck have well recognized familial association. Retroperitoneal paragangliomas are uncommon and we present two cases of familial malignant retroperitoneal paraganglioma. Review of the literature revealed marked differences in the incidence and malignant potential of familial and non-familial paraganglioma. In contrast to the cases reported here, familial tumours are generally benign, though they may occur at multiple sites. Familial and non-familial paragangliomas may indeed be different disease entities.

Adult↗
PubMed1988

Dose response relation to oral theophylline in severe chronic obstructive airways disease.

OBJECTIVE: To evaluate measurement of the trapped gas volume as a measure of respiratory function in patients with chronic obstructive airways disease and their response to treatment with theophylline. DESIGN: Patients able to produce consistent results on testing of respiratory function spent two weeks having dosage of theophylline adjusted to give individual pharmacokinetic data. This was followed by random assignment to four consecutive two month treatment periods--placebo and low, medium, and high dose, as assessed by serum concentrations of theophylline. Respiratory function and exercise performance was assessed at the end of each two month period. SETTING: Chest unit in district hospital. PATIENTS: Thirty eight patients with chronic bronchitis and moderate to severe chronic obstruction to airflow were recruited; 33 aged 53-73 years completed the study. INTERVENTIONS: Dosage of oral theophylline increased during two week optimisation period to 800 mg daily unless toxicity was predicted, when 400 mg was given. Targets for the steady state serum theophylline concentrations were 5-10 mg/l in the low dose period, 10-15 mg/l in the medium dose, and 15-20 mg/l in the high dose period. ENDPOINTS: Respiratory function as measured by forced expiratory volume in one second, forced vital capacity, peak expiratory flow rate, slow vital capacity, and static lung volumes using helium dilution and body plethysmography from which trapped gas volume was derived. Exercise performance assessed by six minute walking test and diary cards using visual analogue scale. MEASUREMENTS AND MAIN RESULTS: The forced expiratory volume in one second, forced vital capacity, and peak expiratory flow rate changed only slightly (about 13%) over the range of doses. There was a linear dose dependent fall of trapped gas volume from 1.84 l (SE 0.157) to 1.42 l (0.152), 1.05 l (0.128), and 0.67 l (0.102) during the placebo and low, medium, and high dose treatment periods. Mean walking distance increased by up to 55.6 m (20%). There was a modest improvement in dyspnoea as the dose of theophylline was increased. Side effects were mostly minor but they became more frequent as the dose was increased. CONCLUSION: The fall in trapped gas volume may reflect an improvement in peripheral ventilation (associated with treatment with theophylline) which is less apparent in the more common tests of lung function used in patients with chronic obstructive airways disease.

Administration, Oral↗
PubMed1988

Polymorphic N-acetylation capacity in lung cancer.

Hepatic N-acetylation phenotype has been suggested to be an important risk factor in the aetiology of bladder cancer. This study explores the N-acetylation capacity of a series of lung cancer cases (126) and two control groups. No overall association of slow or rapid acetylators exists between cancer patients and controls. There is also no difference in the distribution of acetylation phenotypes amongst the histological subtypes.

Acetylation↗
PubMed1988

The accuracy and stability of Bayesian theophylline predictions.

Pharmacokinetic parameters for theophylline were determined in 33 patients (3 women), mean age 61.2 years and weight 74.6 kg using the following three methods: (a) standard one-compartmental model calculations, assuming 100% bioavailability, after a single dose of theophylline syrup (mean dose 413 mg); (b) drug nomogram; and (c) Bayesian analysis. Patients entered a randomised study of three two-monthly dosage regimens using low, medium, and high theophylline twice daily doses. These doses produced mean (+/- SE) steady-state serum theophylline concentrations of 6.3 (+/- 0.4), 12.1 (+/- 0.3) and 18.3 (+/- 0.5) mg/L, respectively. A fourth period of placebo (2-month duration) was also included. At the end of each treatment period the measured serum theophylline concentration of each patient was compared with those predicted by each of the above three methods. The revised estimates derived from Bayesian analysis produced the least biased [mean prediction error (ME)] and most precise (mean squared prediction error) predictions for all three dosage periods. Statistical analysis of relative performance demonstrated that the difference in precision between the revised estimates and those of the other two methods was significant (p less than 0.05) with the magnitude of the difference increasing with dose. The revised estimates were also found to be less biased (p less than 0.05) than those of the nomogram. The ME (+/- SE) of the revised estimates for the low, medium, and high dosage periods was 0.34 (+/- 0.30), -0.02 (+/- 0.22) and -0.48 (+/- 0.31) mg/L, respectively.

Bayes Theorem↗
PubMed1987

Audit of work-load of physicians with a special interest in respiratory medicine.

A 6-month prospective survey was undertaken to assess the work-load of two consultant general physicians with special interest in respiratory medicine, one in a teaching hospital (TH) and the other in a district general hospital (DGH). The two firms dealt with similar numbers of inpatients of whom half had non-respiratory disease. Eighty per cent of the outpatient work of both firms was respiratory disease. The TH firm saw more referrals from other consultants and referred more patients, especially to other physicians. Practical procedures performed, the proportion of patients seen by the consultant at first attendance and the range of both respiratory and general medical conditions seen by the two firms was similar.

England↗
PubMed1987

Neuron-specific enolase as a guide to the treatment of small cell lung cancer.

A retrospective evaluation of serial measurements of neuron-specific enolase (NSE) has been performed in 58 patients with small cell lung cancer (SCLC). All 58 patients received first-line chemotherapy and 11 patients received also second-line treatment after relapse. Samples were obtained every 3-4 weeks during treatment before each cycle of chemotherapy and every 6 or 12 weeks during follow-up. NSE values were depicted on semi-logarithmic paper. Fifty-one times a major response (complete or partial remission) was observed and 49 times the NSE level reached a plateau between 3.5-10 ng/ml. The NSE level did not discriminate between a complete or a partial remission. Seven times stable disease was obtained and the NSE level declined but remained above the normal plateau of 3.5-10 ng/ml. On 50 occasions progressive disease was found. In 3 cases progressive disease was due to a histologically-proven non-small cell lung cancer and NSE levels did not change. In only 5 out of the remaining 47 occasions NSE levels were normal at the time of relapse but rose later in 4. On 42 occasions of progressive SCLC an exponential rise of NSE was found, often within the range of 3.5-20 ng/ml. None of 6 patients, who are still incomplete remission for 1-5 years, showed a consistent rise of NSE. Serial measurements of serum NSE, can predict the occurrence of a major response, stable disease and progressive disease outside the brain with a very high accuracy and seem to be at least a useful addition to standard investigational methods to guide the treatment of SCLC.

Adult↗
PubMed1987

The accuracy of a pharmacokinetic theophylline predictor using once daily dosing.

1. The accuracy of a computer based pharmacokinetic prediction method based on Bayesian analysis has been evaluated for an oral show release form of theophylline. 2. In 83 patients from seven centres 24 h serum theophylline concentration-time profiles were measured under a variety of circumstances. 3. Revised predictions of 24 h serum theophylline concentration profiles were generated by Bayesian analysis using single serum drug concentrations taken before, during and after the study days in different subgroups of those patients. Comparing the predicted and measured profiles the mean prediction error (bias) was 0.05 mg l-1 for peak concentrations and 0.04 mg l-1 for trough concentrations during once daily dosing. The corresponding root mean squared prediction errors (precision) were 2.59 and 1.17 mg l-1, respectively. 4. This accuracy is considered more than adequate for clinical purposes. 5. The technique can be used with a variety of other drugs and can form a valuable part of a routine therapeutic drug monitoring service.

Adult↗
PubMed1987

Doubling time of neuron-specific enolase and survival in small cell lung cancer patients. Results of a preliminary analysis.

During a retrospective analysis of the value of neuron specific enolase (NSE) in patients with small cell lung cancer (SCLC) it became apparent that at progressive disease (PD) NSE rose exponentially with a doubling time (NSE-Td) varying from 10 - 94 days. In this study the influence of the NSE-Td on the survival of 29 SCLC-patients has been investigated. A significant correlation between survival from the start of rise of NSE at PD and NSE-Td was observed. By extrapolating the exponential rise of NSE to the start of treatment a theoretical logarithmic value of NSE, called Yr, could be calculated. When the patients were grouped according to the Yr value greater than -1, between -1 and -4 and less than or equal to -4 a highly significant correlation between the survival from the start of treatment and NSE-Td was found in all 3 groups. These preliminary data suggest that by means of NSE-Td and Yr value the survival of an SCLC-patient from the time of rise of NSE and from the start of treatment may be predicted within certain limits.

Carcinoma, Small Cell↗
PubMed1985

Evaluation of a radioimmunoassay for neuron specific enolase in small cell lung cancer.

A radioimmunoassay for neuron specific enolase (NSE), a marker of neuroendocrine differentiation, has been evaluated in small cell lung cancer (SCLC). In untreated patients 25/38 (68%) with localized SCLC had raised blood levels of NSE (greater than 13 ng ml-1), in extensive disease 34/39 (87%) patients had raised NSE levels. In patients with non-small cell lung cancer (NSCLC) the serum levels were raised in 16/94 (17%). In extensive tumours of non-pulmonary origin NSE levels were increased in 24/116 (20%) patients. Longitudinal studies indicated a good correlation between the response to chemotherapy and fall of NSE levels. Tumour progression was accompanied by a rising NSE in 25/29 patients, with doubling times of 7-90 days. In patients with progression with a normal NSE the recurrence was a NSCLC. Cerebral metastases occurring as the only recurrence during clinical complete remission were not accompanied by a rise of NSE. Serum NSE levels provides a valuable monitor for SCLC during and after chemotherapy.

Carcinoma, Small Cell↗
PubMed1984

Adenosine and hypoxic pulmonary vasodilation.

We have previously shown that after exposure to an inspired O2 tension less than 25 Torr, isolated lungs perfused with autologous blood exhibit vasoconstriction followed by dilation. Because adenosine has been implicated as a mediator of hypoxic vasodilation in the systemic circulation and because the concentration of adenosine in the lung has been shown to increase with hypoxia, we tested the hypothesis that adenosine is the mediator of hypoxic pulmonary vasodilation. We first confirmed that adenosine was a vasodilator in isolated lungs of adult male ferrets. Next we added the enzyme adenosine deaminase (ADase), which inactivates adenosine by converting it to inosine, to the perfusate before exposure to one of two levels of hypoxia [inspiratory PO2 (PIO2) 18 or 0 Torr]. In comparison with untreated lungs, the time course of pulmonary arterial pressure at constant flow in lungs treated with ADase (24 mg protein or 6,000 U) was not different; however, when the vessels were constricted at PIO2 25 Torr, ADase prevented vasodilator responses to adenosine administered into either the perfusate or the airways, indicating penetration of active ADase into the interstitium. Unless adenosine released endogenously into the interstitium during hypoxia was somehow protected from the ADase which reached the interstitium, these results indicate that hypoxic pulmonary vasodilation was not mediated by adenosine.

Adenosine↗
PubMed1983

Cardiac output, pulmonary hypertension, hypoxaemia and survival in patients with chronic obstructive airways disease.

A prospective study of cor pulmonale in 74 patients relates pulmonary haemodynamics to survival. Mean arterial oxygen tension (PaO2) was 7.2 +/- 0.14 kPa and mean arterial carbon dioxide tension (PaCO2) 6.6 +/- 0.12 kPa at entry. Pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR), and cardiac output (CO) sitting and supine and where possible on exercise, were measured every one or two years by a floating catheter technique. Survivors showed very little change in pulmonary artery pressure, pulmonary vascular resistance or cardiac output. Those who did not survive, showed a steady increase of PAP and PVR, whether or not they had received continuous oxygen therapy at home. Cardiac output remained normal or slightly elevated despite increasing pulmonary artery pressure. The relationship between VO2 (minute oxygen consumption) and cardiac output remained within the normal or greater than normal range, even on exercise. Although a deteriorating clinical situation may be paralleled by changes in pulmonary haemodynamics, it is questioned whether such changes are causally implicated in mortality.

Cardiac Output↗
PubMed1982

Comparison of salbutamol given by intermittent positive-pressure breathing and pressure-packed aerosol in chronic asthma.

A double-blind crossover study was performed to compare 4 . 8 mg salbutamol given by pressure-packed aerosol and intermittent positive-pressure breathing nebulization in chronic asthmatic patients. The two delivery techniques produced similar changes in respiratory function and pulse rates. Given equal effect, a high-dose pressure-packed aerosol would have advantages in cost and convenience over nebulization techniques.

Aerosols↗
PubMed1981

Effect of severe hypoxia on the pulmonary vascular response to vasoconstrictor agents.

When isolated blood-perfused pig lungs are exposed to inspired O2 tensions (PIO2) below 30 Torr, hypoxic pulmonary vasoconstriction is transient. To determine whether this transience is caused by a decrease in the amount of ATP available for maintenance of smooth muscle contraction, we compared normoxic (PIO2 = 100 Torr) and hypoxic (PIO2 = 10 Torr) dose-response curves to infusions of prostaglandin F2 alpha (PGF2 alpha), angiotensin II (AII), and potassium chloride (KCl). Hypoxia caused reversible depression of the responses to PGF2 alpha and AII but had no effect on the response to KCl. Because during hypoxia the lung was capable of an undiminished vasoconstrictor response to at least one agent, it seems unlikely that the supply of ATP available for contraction was limiting. The mechanism for the transience of the vasoconstrictor response to low PO2 values and the depression of the response to AII and PGF2 alpha remains unknown, but could involve depression of ATP production sufficient to limit some energy-requiring process other than contraction or release of a vasodilator.

Angiotensin II↗