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Biomedical subjects

D Veale

Publications and source records attributed to D Veale.

At least 109 records · Page 6Linked to original sources
PubMed1990

Management of obsessive-compulsive disorder.

Obsessive-compulsive disorder is an anxiety disorder characterized by compulsive rituals such as excessive washing and repeated checking and phobic avoidance. The treatment of choice is behavioural psychotherapy, namely exposure and response prevention.

Antidepressive Agents↗
PubMed1989

Characterization of epidermal growth factor receptor in primary human non-small cell lung cancer.

Membrane preparations from 36 human non-small cell lung cancers were examined for the expression of epidermal growth factor (EGF) receptors, and comparisons were made between tumor types and stage. Eight normal lung membrane preparations were also examined. The concentrations of EGF receptors were assessed by ligand binding studies using 125I-radiolabeled EGF. In two point saturation experiments using 0.3 nM 125I-EGF incubated with membranes from 35 primary lung tumors, a median of 18 fmol/mg of protein (range, 1.1 to 530) was found. This was significantly greater than binding to eight lung membranes: median, 6.1 fmol/mg of protein (range, 1.0 to 14.5) (P less than 0.02). Scatchard binding curves obtained in 21 of the 36 tumors and seven of eight of the normal lung preparations showed high and low affinity sites for EGF receptors on all but two tumor membranes. The dissociation constant of the high affinity sites was similar on tumor and normal lung membranes: range, 0.75 to 30 x 10(-10) M/liter. However, the tumors had a significantly higher concentration of these receptor sites: median, 30.4 fmol/mg of protein versus a median of 6.2 fmol/mg of protein on normal lung membranes (P less than 0.01). Likewise, there were significantly more low affinity sites on tumors: median, 237 fmol/mg compared to 60.2 fmol/mg on normal lung (P less than 0.01). No differences were found in this analysis between tumors of different histological subtypes or clinical stage. It is possible that the high level of expression of high affinity sites on lung tumors could be used as a target for ligand-complexed drugs.

Carcinoma, Non-Small-Cell Lung↗
PubMed1989

Cisplatin with high-dose infusions of hydroxyurea to inhibit DNA repair. A phase II study in non-small-cell lung cancer.

A total of 45 patients with locally advanced and/or metastatic non-small-cell lung cancer (NSCLC) were treated in a phase II trial with high-dose i.v. infusions of 24 g hydroxyurea over 24 h, with 50 mg/m2 i.v. cisplatin 8 h after the start of hydroxyurea infusion. Hydroxyurea, a cell-cycle-specific inhibitor of ribonucleotide reductase, inhibits DNA repair by depleting nucleotide pools. We gave hydroxyurea to achieve steady-state levels of greater than or equal to 1 mM and to potentiate therapy by inhibiting repair of DNA damage produced by cisplatin. Among 21 patients with squamous cell lung cancer, there were 1 complete response (CR), 2 partial responses (PR) and 3 minor responses (MR). Of 13 patients with adenocarcinoma of the lung, 2 had MRs; of 11 patients with large-cell anaplastic lung cancer, none responded. The dominant toxicity was nausea and vomiting, which was manageable and mainly related to cisplatin. The response rate in squamous cell lung cancer was similar to responses obtained with cisplatin alone. The relative ineffectiveness of high-dose 24-h infusions of hydroxyurea in inhibiting repair of DNA damage produced by cisplatin may be due to the low growth fraction of human NSCLC. The high-dose hydroxyurea approach may be more applicable in tumours with a high growth fraction.

Adenocarcinoma↗
PubMed1989

A prospective randomized comparison of fine needle aspiration biopsy and fibreoptic bronchoscopy in the investigation of peripheral pulmonary opacities.

Twenty-nine patients, aged 66(+/- 7) years with a peripheral pulmonary opacity (mean diameter 3.6 +/- 1.8 cm) believed to be a tumor, were randomly allocated to initial investigation by either fibreoptic bronchoscopy or percutaneous fine needle aspiration biopsy, the latter performed under fluoroscopic control. The patients proceeded to the alternative investigation in the event of the first failing to achieve a diagnosis. Malignancy was confirmed by the initial procedure in 14/15 patients randomized to fine needle aspiration biopsy but only in 1/14 patients randomized to fibreoptic bronchoscopy (P less than 0.01). Overall, these figures were 25/28 fine needle aspiration biopsy and 2/15 fibreoptic bronchoscopy (P less than 0.01). These results confirm the clinical suspicion that fine needle aspiration biopsy is far more likely than fibreoptic bronchoscopy to establish the presence of malignancy in peripheral pulmonary opacities.

Aged↗
PubMed1989

Recent advances in the treatment of small cell lung cancer.

Small cell lung cancer is a rapidly dividing tumour that is susceptible to combination chemotherapy and radiotherapy. Improvements in treatment regimens have resulted in better response rates, but long-term survival has not improved over the past decade.

Carcinoma, Small Cell↗
PubMed1988

Phase 1 study of high-dose hydroxyurea in lung cancer.

The in vitro chemosensitivity of a human lung cancer cell line to hydroxyurea (HU) was measured, and concentrations of 1 mM HU effected 99% inhibition of cell growth. Therefore, infusions designed to achieve serum levels of over 1 mM HU were assessed by escalating doses of hydroxyurea (HU) administered by continuous i.v. infusion at 3-weekly intervals in 18 patients with lung cancer. Dose increments from 24 g in 24 h to 48 g in 48 h were achieved. The dose-limiting toxicity at 48 g in 48 h was myelosuppression. Oral administration of HU did not result in sustained levels comparable to those achieved with continuous infusion. Two patients showed evidence of radiological response after three courses of treatment. Serum HU profiles were monitored after administration i.v. in 26 courses and after administration p.o. in 5 courses of treatment. A mean serum level of greater than 1 mM was achieved by 6 h and then maintained during treatment. The standard error of the mean area under the curve showed an overall 5% variation. HU can be given in doses up to 48 g in 48 h 3-weekly with manageable tissue and bone marrow toxicity, and the in vivo blood levels attained are equal to those necessary for effective cell inhibition in an appropriate in vitro model. This schedule provides a basis for combination studies with other cytotoxics or for use of HU as a DNA repair inhibitor.

Aged↗
PubMed1988

A phase 1 and pharmacokinetic study of didox: a ribonucleotide reductase inhibitor.

A phase 1 study of a new ribonucleotide reductase inhibitor, didox, was performed by administration of escalating doses of the drug by slow i.v. injection. Thirty-four patients with unresponsive metastatic carcinoma received the drug. There were 13 escalations of dosage, from a starting dose of 192 mg m-2 to 10 g m-2. Dose limiting toxicity was encountered at 7.5 g m-2 where disturbances of hepatic and renal function were observed, in addition to severe gastrointestinal toxicity. Pharmacokinetic studies showed that a peak level of didox was achieved within 5 minutes of injection. At 1,728 mg m-2 the data best fitted a 2 compartment open model, with a mean serum alpha t1/2 of 5.2 min, with a beta t1/2 of 41.3 min. Less than 10% of the drug was excreted unchanged in the urine and the majority of this excretion was within 6 h. Didox can therefore be safely given by slow i.v. injection at a dose of 6 g m-2.

Adult↗
PubMed1988

Effects of diazepam and chlormethiazole on ventilatory control in normal subjects.

We have studied the effects of chlormethiazole and diazepam given orally on the ventilatory and mouth occlusion pressure (P0.1) responses to CO2 in a placebo controlled study in 10 healthy volunteers. Diazepam 10 mg produced a significant reduction in both the ventilatory and P0.1 responses to CO2, and this was not associated with any effect on respiratory muscle power. Chlormethiazole 250 mg produced less drowsiness than diazepam 10 mg. Therefore in a subsequent study chlormethiazole 500 mg was compared with placebo. Chlormethiazole in either dose had no effect on CO2 responses or on maximum static respiratory pressures. We conclude that diazepam has a direct depressant effect on chemoreceptors and its effects on indices of ventilatory control are not due to impaired muscle function; chlormethiazole in the doses used has no such effects despite producing drowsiness.

Adult↗
PubMed1988

Prospective evaluation of fine needle aspiration in the diagnosis of lung cancer.

The role of fine needle aspiration biopsy has been assessed prospectively in the diagnosis of discrete lung shadows. A questionnaire was completed before each of 100 biopsies (in 97 patients) to determine the clinician's pretest diagnosis and the likelihood of malignancy. The latter estimates were combined with the previously established sensitivity (71%) and specificity (100%) of the procedure for diagnosing malignancy in the unit to allow calculation in each case of the change in certainty of malignancy as a result of the investigation. Among the 100 biopsies there were 73 true positive and 13 true negative results. There were no false positive results but there were 14 false negatives (cases where malignancy was later proved but where the biopsy did not show unequivocal evidence of malignancy). Among the 27 negative biopsy results the clinician had estimated the likelihood of malignancy as 80% or more in 13 cases. In 11 of these 13 patients the eventual diagnosis proved to be a malignant tumour; on the other hand, six of the 10 patients given a less than 50% chance of malignancy had a benign outcome. A positive biopsy result was therefore quantitively of greatest value when the prior estimate of malignancy was low. In the case of the false negative results the prior probability of malignancy was usually sufficiently high to merit further investigation. It is estimated that the procedure led to the avoidance of thoracotomy in up to 14 of 97 patients.

Biopsy, Needle↗
PubMed1987

Epidermal growth factor receptors in non-small cell lung cancer.

The epidermal growth factor receptor is homologous to the oncogene erb-beta and is the receptor for a class of tumour growth factors (TGF-alpha). The clinical correlations with its expression were studied in 77 non-small cell lung cancers (NSCLC). They were stained for epidermal growth factor receptor (EGFr) by means of an indirect immunoperoxidase technique using a monoclonal antibody against the receptor. Normal lung tissue and normal bronchus were stained for comparison. Cancer tissue showed significantly increased staining compared to normal lung (P less than 0.05). Staining for EGFr in 40 squamous carcinomas was significantly stronger than in 37 specimens of other types of NSCLC (P less than 0.05), and staining in stage three NSCLC was stronger than in stage 1 and 2 (P less than 0.05). These results suggest that the presence of a high intensity of staining for EGF receptor is associated with spread of human non-small cell lung cancer and this receptor may be a suitable target for therapy.

Bronchi↗
PubMed1987

Effects of laser treatment on respiratory function in malignant narrowing of the central airways.

Twenty patients with inoperable carcinoma in the trachea or a main bronchus were investigated before and one and 10 days after treatment with a carbon dioxide laser. Patients were assessed by spirometry, maximum flow-volume loops, and a visual analogue score of breathlessness on a scale from 0 (not at all breathless) to 100 (very breathless). At day 10 mean FEV1 had improved from 51.9% to 62.6% of predicted (p less than 0.02) and mean peak expiratory flow (PEF) from 45.3% to 53.1% of the predicted value (p less than 0.05). Improvements in maximum inspiratory and expiratory flows at 50% vital capacity were not significant but the breathlessness score decreased from a mean of 49.1 to 35.3 (p less than 0.01). Improvements in breathlessness were significantly correlated with increases in FEV1 and PEF. Thirteen of the 20 patients had unilateral tumours with partial or complete occlusion of the main bronchus; in these perfusion and ventilation were assessed by radioisotope scans before and 10 days after treatment. Seven of the 13 patients showed an increase in perfusion of the affected lung after treatment but the improvement was small, with a mean increase in unilateral perfusion in the 13 patients of 2.4% of the total counts. Four patients with no perfusion of the affected side showed no significant improvement after laser treatment. Changes in ventilation scans were similar to those in perfusion. It is concluded that laser treatment improves airway function and dyspnoea in malignant narrowing of central airways and that in unilateral obstruction such treatment results, at best, in a small increase in the contribution of the affected lung to perfusion.

Aged↗
PubMed1985

Survival in second degree atrioventricular block.

Two hundred and 14 patients with chronic second degree heart block were seen and followed up in the Devon Heart Block and Bradycardia Survey between 1968 and 1982. The patients were divided into three groups according to the type of block. In group 1 there were 77 patients with Mobitz type I block (mean age 69 years), in group 2, 86 patients with Mobitz type II block (mean age 74 years), and in group 3, 51 with 2:1 or 3:1 block (mean age 75 years). The five year survival was similar in all groups, being 57%, 61%, and 53% in groups 1, 2, and 3 respectively. The presence or absence of bundle branch block did not appear to influence prognosis. In particular, patients in group 1 without bundle branch block did not fare any better than those in group 2 both with and without bundle branch block. One hundred and three of the patients were fitted with pacemakers, the proportion being greatest in group 2. In each group a significantly larger number of paced patients survived than unpaced. The five year survival for all the paced patients in the study was 78% compared with 41% for the unpaced. Since the paced patients were slightly younger than the unpaced two age matched groups of 74 patients each were selected from the paced and unpaced patients, but the five year survival of those paced was still significantly better. It is concluded that in the patients in the present study chronic Mobitz type I block has a similar prognosis to that of Mobitz type II block. Unpaced patients with both types did very badly, whereas those fitted with pacemakers had a five year survival similar to that expected for the normal population. These results refute the benign reputation of chronic Mobitz type I block and imply that patients with this condition should be considered for pacemaker implantation on similar criteria to those adopted for patients with higher degrees of block.

Adult↗
PubMed1983

Unexplained syncope--a diagnostic pacemaker?

We describe our initial experience with a pacemaker which performs the dual function of registering episodes of cardiac arrest and pacing the heart when necessary. The apparatus has a prolonged escape interval (2.30-2.65 seconds) and is capable of counting up to 128 "events." Twenty-five patients complaining of infrequent episodes of loss of consciousness have been studied. Blackouts ceased and episodes of ventricular standstill were recorded in 14 cases; the unit helped to establish a non-cardiac etiology for the attacks in two cases. It is suggested that a bradycardia-recording facility incorporated into a programmable pacemaker would provide a much needed tool in the diagnosis and management of patients with infrequent episodes of loss of consciousness in whom a cardiac mechanism is suspected but unproven.

Aged↗