Retrospective review of pemetrexed with or without platinum in malignant mesothelioma: The Australian 'Special Access Scheme' experience

Background: Pemetrexed and cisplatin have recently been shown to significantly improve survival compared with cisplatin alone. However, there are only limited data reflecting teaching hospital experience outside a clinical trial. Pemetrexed has only been available in Australia on a restricted basis since 2002. We reviewed our experience of patients treated on the Australian ‘Special Access Scheme’ at three major thoracic oncology units. Methods: Charts were reviewed for all patients enrolled on the scheme. Data was extracted on age, World Health Organization (WHO) performance status, histology, prior therapy, time from diagnosis to starting pemetrexed, chemotherapy (pemetrexed alone or with a platinum), cycle number, response rate, actuarial progression‐free and overall survival. Doses were cisplatin 75 mg/m² or carboplatin AUC = 5 and pemetrexed 500 mg/m² every 21 days. Results: 52 patients (32 male and 20 female) were reviewed. Median age was 58 years and 88% were WHO 0–1. Histology included 54% epithelial, 17% biphasic (epithelial and sarcomatoid) and 21% undefined. The median time from diagnosis to administration of pemetrexed was 145 days. Sixty‐five percent had minimal surgical intervention with video assisted thoracoscopy, pleurodesis and biopsy, while 19% had received prior palliative radiation. Seventy‐one percent were chemotherapy naïve, the remaining 29% having received previous platinum and/or gemcitabine regimens. Twenty‐three percent had pemetrexed alone, 35% in combination with carboplatin and 42% with cisplatin. The median number of cycles was 4 (range 1–13). The response rate was 33%. No toxicity was observed in 20% grade 3–4 toxicity in 10% (majority nausea/vomiting). The median progression‐free and overall survival times from starting pemetrexed were 184 days and 298 days, respectively. Conclusions: Pemetrexed‐based regimens are safe and effective in a community setting in malignant mesothelioma.     

Endothelial, inducible and neuronal nitric oxide synthase in congenital pulmonary lymphangiectasis.

Abnormal growth and development of lymphatic pulmonary structures leads to severe hypoxia in congenital pulmonary lymphangiectasis (CPL). This case study aims to determine the cellular source and topographical distribution of the nitric oxide synthases in CPL. It studies the post mortem tissue of a term newborn with the clinical course and histological findings of CPL and three controls without pulmonary pathology. It was found that endothelial cells of pulmonary arteries and lymphatic structures stained significantly more for endothelial nitric oxide synthase protein in the CPL patient compared to the controls. The authors conclude that synthesis of endothelial nitric oxide synthase is upregulated in vascular and lymphatic endothelial cells in congenital pulmonary lymphangiectasis.     

Accumulation of factors influencing respiratory illness in members of a national birth cohort and their offspring.

STUDY OBJECTIVE--The aim was to investigate predictors of childhood lower respiratory tract illness in two generations, and predictors of adult lower respiratory disorders in the first generation. DESIGN--Data on respiratory health and environmental factors from a national birth cohort study were examined from birth to 36 years. Data were also collected on the parents of the subjects and on the subjects' first born offspring from birth to eight years. Main outcome measures were: reports of lower respiratory tract illness before 2 years; lower respiratory tract illness of a week or more between age 20 and 36 years; regular phlegm production at 25 and 36 years; reports of wheeze or asthma at age 36 years; peak expiratory flow rate (PEFR) at age 36 years measured by nurses during home visits; and mothers' reports of lower respiratory illness in first born offspring before 2 years. SUBJECTS--Subjects were a sample of 5362 single, legitimate births taken from all those occurring in England, Wales, and Scotland in one week in 1946, and studied regularly from birth to age 43 years. Data on the subjects' parents and on their 1676 first offspring born while they were aged 19-25 years were also collected. MAIN RESULTS--Lower respiratory tract illness before 2 years fell from 25% in the population born in 1946 to 13% in their first born offspring. In those born in 1946, poor home environment, parental bronchitis, and atmospheric pollution were the best predictors of lower respiratory illness before 2 years, and these three factors and childhood lower respiratory illness and later smoking were the best predictors of adult lower respiratory tract problems. Risk factors for lower respiratory illness in the offspring were manual social class, parental and grandparental lower respiratory disease, and parental smoking. CONCLUSIONS--Risks for adult lower respiratory problems accumulated in childhood through illness, poor social circumstances, and atmospheric pollution. Smoking exacerbated early life risks and was an independent risk factor. In the offspring generation, parental smoking was a risk factor for early life chest illness, together with parental illness and low social class. Reduction of prevalence in the offspring generation was probably accounted for by improvement in home circumstances, reduced atmospheric pollution, and lower rates of parental lower respiratory illness, but current rates of smoking seem likely to prevent much further reduction in early life lower respiratory illness, and thus in this aspect of risk for subsequent adult lower respiratory problems. The accumulation of risk in childhood and adolescence for later adult problems implies a long time scale for the reduction of adult lower respiratory disorders.     

Measurement of diet in a large national survey: comparison of computerized and manual coding of records in household measures

A diary method using household measures was employed to obtain dietary records in a large national prospective survey and a computer program, DIDO (Diet In Data Out), was designed for direct entry of the diaries. The accuracy of this computerized coding system was examined alongside that of the manual coding used for a similar diary in a previous wave, 7 years earlier, of the same survey. Accuracy was assessed by analysis of the errors in the coded and checked records by stringent re-checking of nominal 2% random subsamples of the diet diaries coded by each method. The mean time to code and check each of the 2086 7-day records in the whole survey using DIDO was 58 minutes (SD 30) compared with reported results of 1–4 hours for manual methods. The mean error rate of computerized coding and checking with DIDO was 2.3% (SD 2.1; range 0–8.9) per diary in the subsample. Correcting these mistakes made insignificant changes to the calculated mean energy and nutrient intakes for the subsample. The percentage of individuals changing to an adjacent third of nutrient distribution after correcting unambiguous errors ranged from none (for alcohol) to 11% (for carbohydrate and calcium intake). The mean error rate on a similar subsample of diaries from the earlier survey which had been coded manually was significantly higher at 5.9% (SD 4.1; range 0–17) per diary. Emphasis is laid on the importance, in coding, of dealing with ambiguities in the subjects' records, since this can affect the accuracy and the precision of the nutrient results obtained. We conclude that the DIDO coding method has the advantages of greater accuracy, speed, consistency and efficient data handling, and affords greater data accessibility for checking, compared with manual systems.     

Anti-basal ganglia antibodies and acute movement disorder following herpes zoster and streptococcal infections.

Anti-basal ganglia antibodies (ABGA) have been associated with poststreptococcal encephalitis similar to encephalitis lethargica (EL). We report two children with parainfectious encephalitis of similar phenotype and IgG ABGA. However, the associated pathogens in the two cases differed; beta-hemolytic streptococcus and herpes zoster. ABGA may not be specific to poststreptococcal encephalitis, but rather a surrogate marker of an inflammatory mediated movement disorder, which may respond to immunotherapy.