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Biomedical subjects

S G Spiro

Publications and source records attributed to S G Spiro.

At least 55 records · Page 3Linked to original sources

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↗

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↗

Metastatic non-seminomatous germ cell tumour and dermatomyositis.

Twenty to thirty percent of cases of dermatomyositis in adults are associated with malignancy. We report a case in which dermatomyositis heralded the development of a testicular germ cell tumour. Germ cell testicular tumours are treatable and our case emphasizes the importance of measuring blood levels of beta-human chorionic gonadotrophin and alpha-fetoprotein and examination of the testes in young males with indications of possible malignancy.

Adult↗

Comparison of bronchodilator responses and deposition patterns of salbutamol inhaled from a pressurised metered dose inhaler, as a dry powder, and as a nebulised solution.

The lung dose and deposition patterns of drug delivered by dry powder inhaler are not known. The effects of inhaling 400 micrograms salbutamol delivered by dry powder inhaler (two 200 micrograms salbutamol Rotacaps), by pressurised metered dose inhaler, and by Acorn nebuliser were studied in nine subjects with chronic stable asthma. Technetium-99m labelled Teflon particles were mixed with micronised salbutamol in the pressurised metered dose inhaler and in the capsules; technetium-99m labelled human serum albumin was mixed with the salbutamol solution for the nebuliser study. The pressurised metered dose inhaler deposited 11.2% (SEM 0.8%) of the dose within the lungs; this was significantly more than the dose deposited by the dry powder inhaler (9.1% (0.6%], but did not differ significantly from the dose delivered by the nebuliser (9.9% (0.7%]. Distribution within the peripheral third of the lung was significantly greater with the nebuliser than with the other two systems; FEV1 improved to a significantly greater extent after inhalation of 400 micrograms salbutamol from the pressurised metered dose inhaler (35.6% from baseline) than from the nebuliser (25.8%) or dry powder inhaler (25.2%). Thus after inhalation of similar doses of salbutamol a larger proportion of drug was deposited within the lungs when it was inhaled from a metered dose inhaler than from a dry powder system; the nebuliser achieved the greatest peripheral deposition. The bronchodilator response seems to depend on the amount of drug within the lungs rather than its pattern of distribution.

Administration, Inhalation↗

Response of the Lambert-Eaton myasthenic syndrome to treatment of associated small-cell lung carcinoma.

We evaluated the outcome in 16 patients with Lambert-Eaton myasthenic syndrome (LEMS) associated with histologically verified small-cell carcinoma (SCC). Thirteen patients received specific tumor therapy (chemotherapy, radiation therapy, or resection) and most also received pharmacologic and immunologic treatment for LEMS. Seven of 11 patients surviving for more than 2 months after tumor therapy showed substantial neurologic improvement (1 patient being in complete remission at 7 years); in 3 of 11 improvement was transient. An EMG index of disease severity (compound muscle action potential amplitude in abductor digiti minimi) was significantly increased at final follow-up (p less than 0.01; n = 11). A pretreatment amplitude greater than 3.0 mV was a good prognostic sign. We conclude that a combined treatment approach in SCC-LEMS usually results in neurologic improvement.

4-Aminopyridine↗

Intensive chemotherapy with autologous bone marrow transplantation for small-cell lung cancer.

Since 1980, 75 patients with small-cell lung cancer (SCLC) have been entered into four consecutive studies of high-dose chemotherapy using autologous bone marrow transplantation (ABMT) to assist haematological recovery. In the first study, 25 patients were treated with cyclophosphamide (160-200 mg/kg) as the sole chemotherapy; in the second (26 patients), the cycle of high-dose cyclophosphamide (with or without 800-1,200 mg/m2 etoposide) was repeated as induction treatment. In the first study, response was high [14 complete responses (CR), 7 partial responses (PR)] but was not increased by repeating the cycle (15 CR, 8 PR), and survival was slightly worse in the second trial. In the third study, 15 patients were treated with doxorubicin, vincristine and etoposide for two cycles and then with 200 mg/kg cyclophosphamide. Although high-dose cyclophosphamide increased the complete response rate, the additional responses were short-lived. In the final study, an attempt was made to increase the initial CR rate by combination chemotherapy using carboplatin (400-600 mg/m2), etoposide (120 mg/m2 x 4) and either high-dose cyclophosphamide (40 mg/kg x 4) or melphalan (140 mg/m2). Although all nine patients responded, none underwent a CR. The long-term survival (up to 7 years) does not appear to be different from that in comparably selected cases treated with conventional chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

Duration of chemotherapy in small cell lung cancer: a Cancer Research Campaign trial.

A total of 610 patients with small cell lung cancer were entered into a randomised trial designed to assess the effect of duration of initial chemotherapy on survival. Patients were randomised to receive either four or eight courses of cytotoxic chemotherapy with cyclophosphamide, vincristine and etoposide and also randomised to receive, on disease progression, either second line chemotherapy (methotrexate and doxorubicin) or symptomatic treatment only. In the whole study 196 (32.1%) had limited disease and 414 (67.9%) extensive disease. During initial chemotherapy the response rate (complete and partial responses) after four courses of treatment was 61% with no significant increase in patients receiving eight courses (63%). In those randomised to receive relapse chemotherapy the response rate was improved slightly for those who had originally received four courses of chemotherapy (25.6%) over those receiving eight (18.7%). The overall results show that of the four possible treatment randomizations, four courses of chemotherapy alone is inferior in terms of overall survival (30 weeks median survival) to the other three treatment options (39 weeks median survival, P less than 0.01). In patients responding to initial chemotherapy the disadvantage of four courses of chemotherapy alone was apparent (median survival of 40 weeks versus 49 weeks, P = 0.003) but not if drug treatment was given on relapse. The study shows that limiting treatment to four courses of chemotherapy alone is associated with inferior survival, but this is not the case if chemotherapy is given at relapse.

Adult↗

Spinal cord compression in small cell lung cancer: a retrospective study of 610 patients.

The records of 610 consecutive patients with small cell lung cancer, treated on a common protocol in a multicentre trial, were reviewed and 24 (4%) cases of spinal cord compression identified. Five hundred patients had isotope bone scans performed at presentation, and in 131 (26%) there was abnormal isotope uptake in the spinal column; only 7% of these patients developed spinal cord compression. However, of the 24 patients who presented with back pain and had a positive bone scan affecting the spine, 36% developed cord compression. Cerebral metastases occurred at some stage in 19.5% of all patients and in 45% of patients with cord compression. The combination of cerebral metastases and a positive bone scan gave a 25% chance of developing spinal cord compression. There were two distinct forms of clinical presentation. Six patients (group A) presented with cord compression: All had back pain and positive bone scans, five out of six had sphincter disturbance, and median survival from cord compression was 30 weeks. Eighteen patients (group B) developed cord compression while on treatment: 28% had positive initial bone scans, 44% back pain and 61% sphincter disturbance, and median survival from cord compression was 4 weeks. Spinal cord compression is an important cause of morbidity and mortality in small cell lung cancer. We suggest that it may be possible to select patients who should receive radiotherapy to the spine to try to prevent the development of this complication.

Adult↗