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Biomedical subjects

D M Geddes

Publications and source records attributed to D M Geddes.

At least 127 records · Page 7Linked to original sources
PubMed1992

Wegener's granuloma. A series of 265 British cases seen between 1975 and 1985. A report by a sub-committee of the British Thoracic Society Research Committee.

In order to describe the British experience of Wegener's granulomatosis Hospital Activity Analysis was used to collect cases diagnosed in England, Wales and Scotland between 1975 and 1985. Where possible clinical details, histological material and chest radiographs were obtained. Two hundred and sixty five patients were considered to have Wegener's granulomatosis. In 109 a single pathologist confirmed the diagnosis by finding both granulomas and vasculitis in biopsy material. The diagnosis was made on clinical grounds or clinical grounds together with histological diagnosis in the local hospital in 156 patients. Wegener's granulomatosis was confined to the lung or upper respiratory tract in 22 per cent of patients and renal disease occurred in 58 per cent. Laboratory tests showed a pattern of mild anaemia, polymorph leucocytosis, eosinophilia and an elevated ESR and hypergammaglobulinaemia, with no specific pattern of changes. Histological confirmation was most frequently obtained by examination of nasal biopsy specimens, but multiple biopsies were often required. Renal biopsies showed focal proliferative glomerulonephritis but granulomatous glomerulonephritis was uncommon. Of available chest radiographs 61 per cent were abnormal, large opacities being most common. Small irregular opacities were found less often and other abnormalities were uncommon. Treatment varied widely and 10 per cent of patients received no drug therapy. This large series illustrates that even without specific treatment, patients with Wegener's granulomatosis can survive for several years and with modern treatment survival for more than a decade is possible. Conclusions about the effectiveness of the various therapies cannot be drawn from this retrospective study. Renal failure and disseminated vasculitis were the commonest causes of death; death was considered to result from complications of treatment with cytotoxic drugs or prednisolone in 6 per cent of patients.

Adolescent↗
PubMed1991

Quality of life in lung cancer.

The prognosis of a patient with lung cancer is poor and the quality is at least as important as the quantity of remaining life. Quality of life is a useful concept which is almost impossible to define but there are a number of important factors which contribute to it. Culture, religion, previous experience and the point of view of the individual all contribute to which of these factors are considered most important. Any quality of life assessment will, therefore, only apply to a defined community. The measurement of quality of life in cancer trials should concentrate on a few important categories such as physical symptoms, psychology and social factors and should be simple rather than comprehensive. In addition, a few frequent measures are better than an occasional comprehensive survey and ideally, both approaches should be combined and compared. Such measurements are most useful for comparative trials rather than for making an overall quality of life estimate. Finally, for routine clinical use outside clinical trials the quality of life index or the Karnofsky scale is recommended.

Aged↗
PubMed1991

A randomised trial of planned versus as required chemotherapy in small cell lung cancer: a Cancer Research Campaign trial.

In a study of chemotherapy as palliative treatment, 300 patients with untreated limited and extensive stage small cell lung cancer (SCLC), who did not have progressive disease after the first cycle of chemotherapy, were randomised to receive either regular 'planned' chemotherapy or chemotherapy given 'as required' (AR). All patients received the same chemotherapy: cyclophosphamide 1 gm m-2 i.v., vincristine 2 mg i.v., and etoposide 120 mg m-2 i.v. on day 1, and etoposide 100 mg b.d. orally on days 2 and 3. Planned chemotherapy was given regularly every 3 weeks. AR chemotherapy was given for tumour-related symptoms, or for radiological progression of disease. Both groups of patients were assessed every 3 weeks and a maximum of eight cycles of chemotherapy was given. A detailed quality of life assessment was made using daily diary cards. The median survival (MS) of patients given AR chemotherapy was not significantly worse than those receiving planned treatment [MS: Planned = 36 weeks (95% C.I. 32-40 weeks), AR = 32 weeks (95% C.I. 28-37 weeks) P = 0.960]. In the AR patients the median interval between treatments was 42 days. On average AR patients received half as much chemotherapy as planned patients. AR patients with a treatment-free interval (TFI) of more than 8 weeks between the first and second cycles of chemotherapy survived longer than those in whom this interval was less than 4 weeks; [MS: TFI greater than 8 = 47 weeks (95% C.I. 32-53 weeks); TFI less than 4 = 24 weeks (95% C.I. 17-34 weeks) P = 0.013]. Contrary to expectation, in the quality of life assessment the AR patients scored themselves as having more severe symptoms than patients receiving planned treatment. AR chemotherapy is a novel method of attempting to use cytotoxic drugs palliatively, which resulted in less drug treatment for approximately equivalent survival. However the palliative effect seen with as required treatment was less satisfactory than with planned chemotherapy.

Aged↗
PubMed1991

Characterization of a Ca(2+)-dependent anion channel from sheep tracheal epithelium incorporated into planar bilayers.

1. Anion-selective channels from the apical membrane of respiratory epithelia are involved in the secretion of chloride into the airway lumen. In cystic fibrosis (CF) there is an abnormality of phosphorylation-regulated chloride transport in this tissue, whilst a calcium-dependent pathway appears to function normally. 2. Using incorporation of apical membrane vesicles into planar phospholipid bilayers, we have characterized the most commonly seen anion-selective channel from sheep tracheal epithelium. 3. In symmetrical 200 mM-NaCl solutions the channel showed rectification, with a chord conductance at negative voltages of 107 pS and at positive voltages of 67 pS. The channel characteristically demonstrated subconductance states at 1/3 and 3/4 of the fully open level. Selectivity for chloride over sodium was approximately 6:1. 4. The channel required a minimum of approximately 100 microM-calcium on the presumed cytoplasmic surface (cis) for opening events to be observed. Open probability (Po) of the fully open state was markedly voltage dependent, but little effect of voltage was seen on the 1/3 subconductance state. 5. The relative permeabilities of monovalent anions monitored under bi-ionic conditions gave the following sequence: NO3- greater than I- greater than Cl- = Br- much much greater than F-. The order of conductances in symmetrical solutions was Cl- = NO3- greater than Br- greater than I- much much greater than F-. 6. The chloride channel blocker 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB) produced a dose-related reduction in Po with a flickering block at 10-50 microM and complete block at higher concentrations. 7. ATP produced a dose-related reduction in Po with effects at 1 microM and complete closing at 1 mM. These effects were only seen with addition to the cis chamber. 8. The catalytic subunit of protein kinase A, either when incubated with vesicles prior to incorporation into bilayers, or when added directly to either chamber, produced no effect. 9. Channels with very similar properties were seen from transfected human tracheo-bronchial cells. 10. Recent whole-cell patch-clamp studies have suggested a distinct calcium-activated chloride current in secretory epithelia. The described channel has properties in common with this current and may be a candidate for its single-channel basis.

Adenosine Triphosphate↗
PubMed1991

Pulmonary deposition of nebulised amiloride in cystic fibrosis: comparison of two nebulisers.

BACKGROUND Preliminary evidence suggests that regular inhalation of nebulised amiloride reduces sputum viscoelasticity, increases the clearance of sputum by mucociliary mechanisms and by coughing and reduces the rate of deterioration in lung function in patients with cystic fibrosis. These effects depend on adequate delivery of amiloride to the airways. This study was performed to quantify and compare pulmonary deposition of amiloride produced by two different nebuliser systems. METHODS The pulmonary deposition of nebulised amiloride (1 mg in 3 ml saline) was measured in eight patients with cystic fibrosis when given via a jet (System 22 with CR 60 compressor) and an ultrasonic (Fisoneb) nebuliser. Human serum albumin labelled with technectium-99m was used as an indirect marker for amiloride and its deposition in the lung was detected with a gamma camera. RESULTS Amiloride inhalation caused no side effects or changes in spirometric indices. The mean (SD) total pulmonary amiloride deposition was 57 (24) micrograms with the System 22 and 103 (53) micrograms with the Fisoneb nebuliser. Pulmonary deposition was completed more rapidly with the Fisoneb (4-5 minutes) than with the System 22 nebuliser (7-8 minutes) and the Fisoneb was preferred by the patients. CONCLUSIONS Both nebulisers appeared to deliver adequate amounts of amiloride to the lungs, but treatment with the Fisoneb nebuliser was quicker, more efficient, and more acceptable to the patients. Of the two nebulisers assessed, the Fisoneb would be preferred for clinical trials.

Administration, Inhalation↗
PubMed1991

BOOP and COP.

BOOP and COP are essentially the same condition and represent one of many ways in which the lung may respond to an inflammatory stimulus. Some underlying causes of BOOP have been identified but in many cases no cause can be found. The clinical and radiological features are of a pneumonic illness that responds to corticosteroids rather than antibiotics, but as milder cases are being identified the clinical spectrum is widening. Most cases can be confidently diagnosed only by open lung biopsy, but bacteriological lavage and transbronchial biopsy followed by a trial of steroids may sometimes be considered.

Bronchiolitis Obliterans↗
PubMed1991

Effect of heart-lung transplantation on airway potential difference in patients with and without cystic fibrosis.

Measurement of the potential difference (PD) across the airways provides an indication of the viability and integrity of the lining epithelium. PD was recorded from the lower airways in "diseased controls" and in patients following heart-lung transplantation. Diseased controls showed a high PD centrally which fell (became less negative) peripherally (trachea -15.8 mV (SEM 1.0), lobar bronchi -12.6 mV (1.2), segmental bronchi -9.8 mV (1.2]. Following heart-lung transplantation (HLT) the profile of PD with airway size was altered in comparison to non-transplanted patients with reduced values in the large airways. Host tracheal values above the anastomosis were similarly reduced. Two episodes of rejection were associated with a lower mean airway PD; no significant changes were found with infection. In patients with cystic fibrosis (CF), values in the donor lung did not differ from those in non-CF transplanted patients up to one year following transplantation, although nasal PD in the host remained elevated. HLT selectively alters the PD profile only of larger airways, which may relate to the interruption of the bronchial arterial supply to these sites.

Biological Transport, Active↗
PubMed1990

Randomised, double-blind, placebo-controlled trial of methotrexate in steroid-dependent asthma.

69 patients with steroid-dependent asthma (mean daily prednisolone dose 14.2 [SD 6.1] mg) took part in a randomised, double-blind, placebo-controlled study of 24 weeks' treatment with methotrexate 15 mg weekly. The patients were seen every 4 weeks by the same physician, who reduced the daily prednisolone dose by 2.5 mg if the daily diary card variables and measurements of lung function were unchanged or improved. All other treatment remained unchanged. After 24 weeks of treatment the prednisolone dose had been reduced by a significantly greater proportion in the methotrexate than in the placebo group (50% vs 14%) and the reduction was not sustained after the study treatment stopped. There were substantial abnormalities in liver function tests in 5 of the 38 patients taking methotrexate.

Administration, Oral↗
PubMed1990

Infection v. colonisation.

The interaction between bacteria and the human respiratory tract is complex and while the concept of three states, namely sterility, colonisation, and infection is clinically convenient it is inevitably in oversimplification. Evidence from both clinical and laboratory observations has led to some ideas about the relationship between colonisation and infection and while these are helpful in defining the steps involved, the decision of whether and when to start new treatment remains one of clinical judgement. This article reviews the evidence from lung disease both in and out of an intensive care unit and attempts to define the frontier between infection and colonisation in different clinical settings.

Bacterial Adhesion↗
PubMed1990

Quality of life during chemotherapy for small cell lung cancer: assessment and use of a daily diary card in a randomized trial.

Fifty-three patients who were taking part in a randomized trial of chemotherapy in small cell lung cancer (SCLC) were entered into a study of quality of life measurement using a daily diary card. Patients received either four or eight cycles of initial chemotherapy and daily records were scored, using a four point scale of nausea, sickness, appetite, sleep, mood, pain, activity and general well being. Two hundred and fifty-six of a possible 379 cards were returned (68% compliance). The first 31 patients took part in an assessment of the diary card where comparison was made with nurse ratings using the card, the EORTC questionnaire and the Spitzer quality of life index. These comparisons showed appropriate convergent and divergent validity and demonstrated the sensitivity of the diary card to short term changes compared with the other measures. In the randomized trial the diary card demonstrated a worsening of sickness and related variables as treatment continued. This spilled over into mood and general well being although physical variables of pain, sleep and activity were largely unaffected. Prophylactic cranial irradiation was associated with a transient increase in sickness and vomiting. The study shows that the diary card is an instrument sensitive to short term changes in quality of life and thus especially useful for comparing effects during the period of treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

The response of cerebral metastases in small cell lung cancer to systemic chemotherapy.

Although small cell lung cancer (SCLC) is very chemosensitive, cerebral metastases are treated with radiotherapy in the belief that they are protected from chemotherapy by the blood-brain barrier (BBB). The validity of this assumption has not been tested in clinical practice. In a randomised trial of treatment in 610 patients with SCLC, 19 patients who had symptomatic cerebral metastases at presentation were treated initially with chemotherapy, and cranial irradiation withheld. Chemotherapy was cyclophosphamide 1 g m-2 i.v. day 1, vincristine 2 mg i.v. day 1 and etoposide 100 mg tds p.o. days 1-3, repeated every 21 days, with response assessed objectively by computerised tomography (CT) or radionuclide brain scan, and by clinical examination. A post-chemotherapy scan was obtained in 14 patients, eight of whom achieved a partial remission and one a complete remission of the cerebral metastases. The radiologically proven responses were sustained and accompanied by rapid neurological improvement. Of the remaining five patients who were assessed by clinical examination alone, one had improved neurological function after chemotherapy. The response rate for SCLC cerebral metastases treated with chemotherapy was therefore 10/19 (53%). Chemotherapy has the advantage over cranial irradiation of simultaneously treating both cerebral metastases and extracranial disease. The place of chemotherapy in the management of cerebral metastases in this and other chemosensitive tumours should be reconsidered since these findings indicate that the BBB does not prevent response to chemotherapy.

Adult↗