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.     

Lack of effects of prenatal exposure to lidocaine on development of behavior in rats

The objective of this investigation was to study the effects of lidocaine upon postnatal development of the rat. Lidocaine, 6 mg/kg (21 mumol/kg), was given to a group of 12 rats. Injections were administered intramuscularly, bilaterally in the masseter muscles, once a day on days 10 and 11 of pregnancy. Twelve control rats were given physiologic saline. Clinical signs, mortality, body weight, and food consumption were recorded during pregnancy and lactation. The duration of gestation was also recorded. The development of the offspring was monitored by tests of spontaneous activity, nociception, learning ability, and physical development. No clinical signs of adverse reactions were seen in any of the groups. In the majority of the learning ability tests, the control and lidocaine-treated groups showed similar results. However, in the schedule of differential reinforcement of low rates of responding (DRL 20), the lidocaine-exposed males received more reinforcements than the controls and made fewer responses. In the tests of nociception, a significant difference between sexes was recorded, in that the females were more sensitive than the males in the shock-titration test. Physical development, as monitored by swimming ability and spontaneous activity, showed no inter-group difference. The present results indicate that prenatal exposure to lidocaine fails to result in postnatal impairment of the development of behavioral performance of a wide range of tasks.     

Vestibular-nerve inputs to the vestibulo-ocular reflex: a functional-ablation study in the squirrel monkey

Advantage was taken of differences in the electrical excitability of vestibular-nerve fibers to characterize the afferent input to the canal-related vestibulo-ocular reflex. Large anodal (inhibitory) currents, when delivered to both ears, result in a selective, reversible ablation of irregular afferents. Their background discharge and responses to head rotations are temporarily abolished. The same currents have less effect on the background discharge and no effect on the rotational sensitivity of regular afferents. Eye movements were evoked by head rotations in alert monkeys. The ablating currents did not alter the ocular responses to sinusoidal head rotations in yaw or pitch planes. Responses to rapid changes in head velocity were similarly unaffected. It is concluded that irregular afferents do not make a net contribution to the reflex. Slow-phase eye movements evoked by unilateral galvanic currents are consistent with this conclusion. The results are incorporated into a systems model of the reflex. There are three conclusions from the model: (1) the signal to motoneurons consists of the sum of three components related, respectively, to head velocity, eye position, and filtered eye velocity; (2) regular afferents provide the best match to the dynamic requirements of the reflex; and (3) the central pathways responsible for all three signal components receive regular inputs.