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.     

Association of polymorphonuclear leukocytes with sites of aortic catheter-induced injury in rabbits

The kinetics of the association of polymorphonuclear leukocytes (PMNs) with arterial balloon catheter-induced injury have been examined. An average of 6 X 10(7) PMNs were isolated from 20 ml of blood and labelled with 111In-oxine for reinfusion into the donor rabbit. The cells remained viable as demonstrated by both in vitro and in vivo tests of cell function. The abdominal aorta of rabbits was denuded of endothelium and immediately, 24 h, or 5 weeks later, exposed to autologous radiolabelled PMNs for 1 h. The presence of PMNs at sites of denudation was demonstrated by detection of the radioactive label and was confirmed by light and electron microscopy after 24 h, but not at 5 weeks. Immediately following denudation radioactivity was 2.44 +/- 0.33 times control (P = 0.006); 2.52 +/- 0.18 at 24 h (P = 0.005); and 1.88 +/- 0.32 times control at 5 weeks (P = 0.045). The presence of PMNs, or their products, 5 weeks after denudation suggests a more complex role of PMNs and possibly a direct involvement in the long term changes resulting from arterial balloon catheter injury.     

The fluosol-perfused isolated canine pancreas: a model for the study of blood component effects in acute pancreatitis

Blood components have been implicated as factors which modulate organ injury in acute pancreatitis. To isolate these effects we compared a standardized isolated, blood-perfused, canine pancreas model as described by Herman-Taylor and modified by Cameron with a model using fluosol, a fluorocarbon, as the perfusate. Pancreatitis was induced using partial pancreatic duct obstruction with secretin induced hypersecretion. Twenty-four dogs were randomized into four groups; (1) blood-perfused control (BPC), (2) fluosol-perfused control (FPC), (3) blood-perfused injury (BPI), (4) fluosol-perfused injury (FPI). All glands were observed for 4 h for mean arterial pressure (MAP), weight gain, gross appearance, and venous amylase. Stability was monitored with blood gases and glucose. Specimens were taken at 4 h for light and electron microscopy. Results: BPI preps had a significantly higher vascular resistance at 3 and 4 h compared to FPI preps (3.85 vs 3.26 PRU and 4.8 vs 3.9 PRU, respectively) (P less than 0.002). Edema formation (3+ vs 1+) and venous amylase (18,543 vs 1961) (P less than 0.001) were greater in BPI than FPI preps. Light and electron microscopy confirmed injury but could not quantify it between injury groups. Summary: Hypersecretion and partial ductal obstruction causes a more severe injury in the blood than the fluosol perfused preparation. Changes in the peripheral resistance seen in the blood perfused model lend support to the theory that the primary injury in this model is at the capillary level and is modulated by a blood component.     

Longitudinal,population-based study of racial/ethnic differences in colorectal cancer survival: impact of neighborhood socioeconomic status,treatment and comorbidity

Background  

Colorectal cancer, if detected early, has greater than 90% 5-year survival. However, survival has been shown to vary across racial/ethnic groups in the United States, despite the availability of early detection methods.     

Period, age, and cohort effects on substance use among young Americans: a decade of change, 1976-86

In an earlier article in this Journal, we reported analyses that differentiated among period, age, and cohort effects on substance use among American youth 18 to 24 years old, from the high school classes of 1976 to 1982 during the period of 1976 to 1982. The present analyses extend the classes and years to 1986, and the age range to 18-28. A cohort-sequential design is employed, based on annual surveys of nationally representative samples of high school seniors, plus annual follow-up surveys of each senior class. Twelve different classes of drugs, both licit and illicit, are examined. Several different types of period, age, and cohort effects over the last decade are identified. Alcohol use (monthly and occasions of heavy use), and the use of marijuana, cocaine, amphetamines, methaqualone, barbiturates, LSD, psychedelics other than LSD, and tranquilizers all showed period effects. Occasions of heavy drinking, cigarette smoking, monthly and daily use of alcohol, and annual prevalence of cocaine, amphetamines, barbiturates, LSD, and narcotics other than heroin showed age effects. Class effects were seen for cigarette smoking and daily marijuana use.