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Biomedical subjects

S G Spiro

Publications and source records attributed to S G Spiro.

At least 37 records · Page 2Linked to original sources

Lung deposition patterns of directly labelled salbutamol in normal subjects and in patients with reversible airflow obstruction.

BACKGROUND--Earlier studies of aerosol deposition in the lungs have relied on indirect labelling of Teflon spheres of a similar size distribution to the drug in question and have assumed similar aerodynamic properties. Using a modification of a new technique for directly labelling salbutamol, the deposition of salbutamol within the lungs of normal subjects and patients with asthma has been studied with the use of a metered dose inhaler (MDI) alone, an MDI with a spacer device, and a dry powder inhaler (DPI). METHOD--Salbutamol was directly labelled with technetium-99m and placed in an MDI or DPI. Ten normal subjects and 19 patients with asthma inhaled 200 micrograms of salbutamol by means of the MDI alone, the MDI with a spacer device attached, and by DPI on separate days. Deposition was assessed by a dual headed gamma camera after inhalation of the drug. RESULTS--The total mean (SD) percentage deposition of the drug in the normal subjects was 21.6% (8.9%) with the MDI alone, 20.9% (7.8%) with the MDI with spacer, and 12.4% (3.5%) with the DPI. For the patients, the mean percentage deposition was 18.2% (7.8%) with the MDI alone, 19.0% (8.9%) with the MDI and spacer, and 11.4% (5.0%) with the DPI. Bronchodilatation achieved by the patients was similar with all three techniques. Mean peripheral lung deposition was significantly greater with a spacer device than when the MDI was used alone in both normal subjects (49.4% (6.1%) v 44.1% (9.9%)) and patients (38.6% (11.1%) v 30.4% (9.4%)). CONCLUSIONS--The deposition of directly labelled salbutamol from an MDI is greater than previously estimated by indirect labelling techniques. The deposition of labelled salbutamol from a DPI, however, is little different from that measured by indirect techniques.

Adult↗

Value of pulse oximetry in screening for long-term oxygen therapy requirement.

Pulse oximetry, combined with spirometry, was evaluated as a method of selecting chronic obstructive pulmonary disease (COPD) out-patients requiring definitive arterial blood gas analysis for long-term oxygen therapy (LTOT) assessment. A relatively high screening arterial oxygen saturation by pulse oximetry (SaO2) level was set, in order to maximize sensitivity. All 113 COPD out-patients attending the hospital clinic over a 6 month period were screened. Sixty had a forced expiratory volume in one second < 1.5 l and 26 had an SaO2 < or = 92%. These 26 underwent arterial blood gas analysis. Nine had an arterial oxygen tension < 7.3 kPa all with an arterial carbon dioxide tension (PaCO2) > 6 kPa. A further eight had a PaO2 < 8 kPa. This produced a sensitivity of 100% and specificity of 69% for oximetry in the detection of PaO2 < 7.3 kPa determined by direct arterial puncture and 100% and 86% respectively for detecting a PaO2 < 8 kPa. Although the poor specificity of oximetry in the crucial PaO2 range makes it unsuitable, when used alone, for prescription of LTOT, it may prove valuable in selecting patients who require further definitive arterial blood gas analysis.

Aged↗

Phase II study of Edatrexate in stage III and IV non-small-cell lung cancer.

A total of 49 patients with advanced, previously untreated non-small-cell lung cancer (NSCLC) were treated with a new antifolate, Edatrexate (10-ethyl-10-deaza-aminopterin; 10-EdAM). Patients received 80 mg/m2 weekly for 12 weeks, and responders received a further 6 cycles at 2-week intervals. Dose reductions were carried out for haematological toxicity and mucositis. Response was assessed prior to each treatment according to WHO criteria. Among the 45 evaluable patients, 6 [13.3%; 95% confidence interval (CI), 6%-26%] achieved a partial response (PR) and 9 (20%; 95% CI, 11%-34%) showed a minor response (MR; 25%-50% reduction in the sum of 2 perpendicular tumour diameters). In those receiving four or more cycles of treatment, the PR and MR rates were 17.6% and 26.4%, respectively. The resultant toxicity mainly constituted skin rash, mucositis and myelosuppression. Edatrexate is active against NSCLC and produces toxicity profile similar to that of methotrexate.

Aged↗

The value of CT scanning and percutaneous fine needle aspiration of adrenal masses in biopsy-proven lung cancer.

Pre-operative CT scans of 546 patients with biopsy-proven primary bronchial carcinoma were reviewed. Twenty-two patients had a solid adrenal tumour (2 bilateral). Sixteen underwent percutaneous fine needle aspiration (FNA). Malignant cells were aspirated in five, eight revealed benign cells and in three cases there was insufficient material for diagnostic purposes. Six patients did not undergo FNA, four of these were considered to have benign adenomas on CT. This was confirmed by the unchanged CT image at more than 21 months follow-up. The five subjects with FNA-proven metastases died at a median of 14 months (range 3-24 months). All five would have been regarded as operable on their staging chest CT scan. Five patients with a negative biopsy underwent surgery, two died of metastases at 6 and 11 months respectively and one died of post-operative complications. The other two have unchanged adrenal lesions on CT at 9 months and 25 months. The CT appearances of these lesions were analysed. Well defined, low attenuation lesions which had a smooth attenuation rim or only involved part of the gland were benign and the survivors had unchanged CT appearances at follow-up (six lesions in five patients). Of these four lesions were less than or equal to 2 cm in diameter. Low attenuation lesions without a rim were malignant (n = 2). These latter both measured more than 2 cm in diameter. The CT appearances of many adrenal lesions were insufficiently distinctive to exclude malignancy and biopsy was necessary to establish a diagnosis.

Adrenal Gland Neoplasms↗

Easy bruising as a side-effect of inhaled corticosteroids.

We wished to determine the prevalence of easy bruising in patients taking inhaled corticosteroids (ICS) compared with those who do not. Differences in age, dosage and duration of use of ICS between patients who bruised and those who did not were also investigated. Confidential questionnaire surveys were conducted over a 6 month study period amongst patients attending a respiratory out-patient clinic and taking regular ICS, and a control group of patients attending non-respiratory clinics and not taking any form of corticosteroids. Patients with bleeding disorders or taking oral steroids, non-steroidal anti-inflammatory drugs or anticoagulants were excluded from the study. Questionnaires from 202 respiratory patients using ICS (group A) were compared with 204 non-ICS patients (Group B) of similar age and sex distribution. Significantly more patients in Group A reported easy bruising than in group B (47 vs 22%, relative risk 2.18, 95% confidence interval (95% CI) 1.62-2.94), and it was the commonest reported symptom. In Group A, the patients that reported easy bruising tended to be older (61 vs 52 yrs), on higher daily dosages (1,388 vs 1,067 micrograms) and had been taking inhaled corticosteroids for longer (55 vs 43 months) than non-bruisers. Overall, females reported easy bruising more frequently than males in both groups. However, comparing Group A with Group B, males taking ICS had a higher relative risk for bruising than females (males, relative risk 5.80, 95% CI 2.38-14.13; females, relative risk 1.80, 95% CI 1.32-2.44).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

Sequential chemotherapy in good-prognosis patients with small-cell lung cancer.

A sequential combination chemotherapy regimen was evaluated in 23 patients with small-cell lung cancer (16, limited disease; 7, extensive disease). All patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, normal serum sodium and albumin levels and alkaline phosphatase values of less than 1.5 times the upper limit of normal. Treatment comprised ifosfamide and either vindesine or vincristine given on weeks 0, 2 and 4; cisplatin and etoposide given on weeks 6, 9 and 12; and doxorubicin and methotrexate given on weeks 15 and 17. The overall response rate at the end of chemotherapy was 91% and the complete response rate was 43%. Treatment was generally well tolerated and the delivered dose intensity was 83% of that projected. Median survival was 54 weeks, with 4 patients (17%) being alive 2 years after the completion of therapy.

Adult↗

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↗

Sternomastoid muscle twitch maximum relaxation rate: prolonged slowing with fatigue and post-tetanic acceleration.

1. The maximum rate of relaxation of stimulated twitches (twitch maximum relaxation rate) of the sternomastoid muscle was compared with its frequency-force curve (expressed as the ratio of force produced at a stimulation frequency of 20 Hz to that produced at 50 Hz, the 20:50 ratio) before and after fatiguing exercise of the sternomastoid muscle in 10 normal subjects. The mean (+/- SEM) fresh state twitch maximum relaxation rate was 9.51 (+/- 0.64)% force loss/10 ms and the mean (+/- SEM) 20:50 ratio was 73.4 (+/- 2.6)%. 2. The mean twitch maximum relaxation rate fell to 71.5 (+/- 2.2)% of the pre-fatigue value at 2 min after exercise, recovering to 73.1 (+/- 1.6)% by 5 min, 78.4 (+/- 2.34)% by 10 min and 80.6 (+/- 2.70)% by 60-min. The 20:50 ratio fell to 72.3 (+/- 3.56)% of pre-fatigue levels at 10 min after exercise and recovered to 78.8 (+/- 3.16)% by 60 min. There was no significant difference in the percentage falls between the two techniques. 3. Further studies were performed to determine the response of the twitch maximum relaxation rate to a prior brief tetanic stimulus or a brief maximal voluntary contraction of the muscle. Both tetanic stimulation and maximal voluntary contraction accelerated the twitch maximum relaxation rate to over 140% of the fresh state value. Both manoeuvres temporarily returned the slowed twitch maximum relaxation rate after fatiguing exercise back to the fresh state value. 4. The effect of fatiguing exercise on the time course of recovery of quadriceps twitch maximum relaxation rate was also studied in two subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Neurological paraneoplastic syndromes in patients with small cell lung cancer. A prospective survey of 150 patients.

One hundred and fifty patients presenting with small cell lung cancer (SCLC) to chest physicians, were assessed neurologically. Neuromuscular or autonomic deficits were common and occurred in up to 44% of cases. Weakness, dry mouth, and weight loss were not mutually independent and may represent the syndrome formerly described as carcinomatous neuromyopathy. By contrast, undoubted paraneoplastic syndromes were much less commonly detected. Two patients had the Lambert-Eaton myasthenic syndrome (LEMS) and one had subacute sensory neuropathy (SSN). In these patients, neurological symptoms antedated other manifestations of cancer, by between six and 17 months. The 95% confidence interval for the prevalence of LEMS or SSN among SCLC patients was 0-4%, consistent with the results of previous retrospective or smaller studies: summing these, the overall prevalence of LEMS among SCLC patients is close to 3%, which implies about 250 new cases per annum in England and Wales. If LEMS and SSN are the least uncommon neurological paraneoplastic syndromes in SCLC patients, this may reflect the accessibility of motor nerve terminals and dorsal root ganglia to cross-reactive anti-tumour cell antibodies.

Carcinoma, Small Cell↗

Melioidosis in a patient from Bangladesh.

A 54 year old Bangladeshi man presented with a history and chest X-ray appearances suggestive of pulmonary tuberculosis. Following deterioration 4 weeks later, he required ventilation. Although a blood culture isolate was subsequently found to be Pseudomonas pseudomallei, it was initially misidentified and dismissed as a contaminant. Further cultures demonstrated the organism, but the patient died, despite treatment with ceftazidime. The case illustrates the importance of taking a detailed travel history and having a high index of suspicion in patients from South East Asia and the Indian sub-continent, including Bangladesh, where the disease has not previously been considered endemic.

Bangladesh↗

Long term effects of smoke inhalation in survivors of the King's Cross underground station fire.

BACKGROUND: In most accidents causing smoke inhalation only a few victims actually inhale the smoke. The fire at King's Cross provided an opportunity to assess the long term effects of smoke inhalation in a larger number of patients. METHODS: Fourteen survivors from the King's Cross underground station fire were assessed for respiratory disability six months after the disaster and 10 were reassessed at two years. All had inhaled substantial quantities of smoke and 10 had skin burns of differing severity. RESULTS: Six months after the fire nine survivors admitted to one or more symptoms, which included hoarseness (two cases), cough (five cases), and breathlessness (six cases); and a survivor with asthma noted a worsening of his symptoms. The remaining five denied new symptoms. Peak expiratory flow, spirometric indices, and transfer factor for carbon monoxide were within the predicted normal ranges. The mean residual volume, however, was greater than the predicted value and the mean maximum expiratory flow at 25% of vital capacity (V25) less than predicted, with no significant differences between smokers (n = 7) and non-smokers (n = 7). At least one of these ventilatory defects, suggesting small airways obstruction, was present in 11 survivors at six months and they had persisted in the seven patients who were reassessed at two years. CONCLUSION: Smoke inhalation may be associated with injury to the small airways.

Adult↗

Intensive weekly chemotherapy for good-prognosis patients with small-cell lung cancer.

A weekly, intensive chemotherapy regimen has been used to treat 70 patients with small-cell lung cancer (SCLC). Forty-five patients had limited disease (LD) and 25 extensive disease (ED) with good prognostic features. The regimen consisted of cisplatin 50 mg/m2 intravenously (IV) day 1 and etoposide 75 mg/m2 IV days 1 and 2, alternating weekly with ifosfamide 2 g/m2 IV day 8 and doxorubicin 25 mg/m2 IV day 8, for a total of 12 weeks. Dose modifications were made according to defined hematologic criteria. Responding patients with limited disease subsequently received mediastinal radiotherapy. Overall response to chemotherapy was 91% with a complete response (CR) rate of 50%. Forty-five patients with limited disease (LD) achieved an overall response rate of 91% with a CR rate of 51%, and 25 patients with extensive disease (ED) achieved an overall response rate of 92% with a CR rate of 48%. Median survival for the whole group was 54 weeks (LD, 58 weeks; ED, 42 weeks). Hematologic toxicity was predictable, without the wide fluctuations in WBC count seen in conventional 3-weekly regimens. In all, one quarter of treatment courses were delayed, most frequently because of leukopenia. Dose reductions were required in 63% of cases. The average delivered dose intensity was calculated and shown to be 73% of projected. Nonhematologic toxicity was mild with nausea and vomiting being the most common. This weekly schedule of chemotherapy has proved to be active and well tolerated and is currently being compared with conventional 3-weekly chemotherapy in a randomized study.

Adult↗

Mitomycin, ifosfamide and cisplatin in non-small-cell lung cancer.

Chemotherapy with mitomycin C, ifosfamide and cisplatin (MIC) is reported to produce responses of 56% and 69% in inoperable non-small-cell lung cancer (NSCLC). We evaluated the regimen in 45 similar patients who received up to six courses of 6 mg/m2 mitomycin C, 3 g/m2 ifosfamide, and 50 mg/m2 cisplatin every 3 weeks. In all, 18 patients had limited disease (LD) and 27 had extensive disease (ED). A total of 18 patients responded (40%), 9/18 with LD and 9/27 with ED; there were 4 complete responders. The median duration of response was 25 weeks, and median survival was 32 weeks (range, 2-96 weeks). Toxicity was moderate. Nausea and vomiting were controlled with i.v. dexamethasone and high-dose metoclopramide. Other toxicities included myelosuppression and alopecia. This study confirms that MIC is one of the most active regimens for treatment of NSCLC, with acceptable toxicity.

Adult↗

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↗