Self-reported symptom experience of critically ill cancer patients receiving intensive care.

OBJECTIVE: To characterize the symptom experience of a cohort of intensive care unit (ICU) patients at high risk for hospital death. DESIGN: Prospective analysis of patients with a present or past diagnosis of cancer who were consecutively admitted to a medical ICU during an 8-month period. SETTING: Academic, university-affiliated, tertiary-care, urban medical center. PATIENTS: One hundred cancer patients treated in a medical ICU. INTERVENTION: Assessment of symptoms. MEASUREMENTS: Patients' self-reports of symptoms using the Edmonton Symptom Assessment Scale (ESAS), and ratings of pain or discomfort associated with ICU diagnostic/therapeutic procedures and of stress associated with conditions in the ICU. MAIN RESULTS: Hospital mortality for the group was 56%. Fifty patients had the capacity to respond to the ESAS, among whom 100% provided symptom reports. Between 55% and 75% of ESAS responders reported experiencing pain, discomfort, anxiety, sleep disturbance, or unsatisfied hunger or thirst that they rated as moderate or severe, whereas depression and dyspnea at these levels were reported by approximately 40% and 33% of responders, respectively. Significant pain, discomfort, or both were associated with common ICU procedures, but most procedure-related symptoms were controlled adequately for a majority of patients. Inability to communicate, sleep disruption, and limitations on visiting were particularly stressful among ICU conditions studied. CONCLUSIONS: Among critically ill cancer patients, multiple distressing symptoms were common in the ICU, often at significant levels of severity. Symptom assessment may suggest more effective strategies for symptom control and may direct decisions about appropriate use of ICU therapies.

Increased release of dopamine in vivo by BMY-14802: contrasting pattern to clozapine.

In preclinical studies, BMY-14802 [alpha-(fluorophenyl)-4-(5-fluoro-2-pyramidinyl)-l-piperazine-buta nol], a potent sigma ligand, exhibited a profile similar to clozapine, an atypical antipsychotic agent. Several atypical antipsychotics have previously been demonstrated to increase dopamine (DA) metabolism without altering DA release in vivo, suggesting a potential mechanism for their lack of extrapyramidal side effects. BMY-14802 increased DA metabolism and release while clozapine increased DA metabolism but decreased DA release in the mouse. This is the first demonstration of a sigma ligand mediated DA release in vivo. The lack of extrapyramidal side effects, despite the enhanced DA release in vivo after BMY-14802 suggests that the atypical profile of clozapine can not be explained by its depressant actions on DA release alone.

The polyamines, spermine and spermidine, negatively modulate N-methyl-d-aspartate (NMDA) and quisqualate receptor mediated responses in vivo : Cerebellar cyclic GMP measurements.

The effects of the polyamines, spermine and spermidine on basal and d-serine-, harmaline- and quisqualate-induced cyclic GMP (cGMP) were measured in mouse cerebellum. Spermine and spermidine at 200 ?g/mouse, intracerebellar injection (icb), did not alter basal cGMP levels. d-Serine (200 ?g/mouse, icb) and quisqualic acid (5 ?g/mouse, icb) caused 5- and 15-fold increases in cGMP. These increases were significantly reversed by co-injected spermine and spermidine (200 ?g/mouse, icb). Furthermore, direct intracerebellar spermidine (200 ?g) completely reversed harmaline (100 mg/kg, sc) induced increases in cGMP. These data indicate that the polyamines, spermine and spermidine attenuate responses mediated through the N-methyl-D-aspartate (NMDA), NMDA-associated glycine receptor and quisqualate receptors. These results provide an in vivo neurochemical evidence for polyamine modulation of excitatory amino acid receptors. Due to their putative abilities to increase mitochondrial uptake of [Ca(+2)], spermine and spermidine are likely to modulate the responses of several excitatory amino acid agonists. The polyamines spermine and spermidine are widely distributed in neural and non-neural tissues and have been shown to play a key role in cell differentiation and growth (Kremzner et al ., 1970; Harik and Snyder, 1974; Raina and Janne, 1975; Seiler, 1981; Pegg and McCann, 1982). Extensive studies have indicated an important role of the polyamines, spermine and spermidine, in the regulation of intracellular [Ca(+2)] levels (Nicchitta and Williamson, 1984; Iqbal and Koenig, 1985; Jensen Lynch and Baudrey, 1987; 1989 a, b). The precise regulation of intracellular [Ca(+2)] levels and maintenance of [Ca(+2)] gradients across the cell membranes are essential in cell survival as prolonged and excessive exposure to calcium can result in neuronal injury and death (Farber, 1981; Rasmussen and Barnett, 1984). The excitatory amino acid glutamate is known to interact with three subclasses of receptors, N-methyl-D-aspartate (NMDA), quisqualate and kainate (Cotman and Iversen, 1987). The role of excitatory amino acids in the etiology of ischemic neuronal death is also well established (Cotman and Iversen, 1987). Although the precise mechanisms of ischemic injury are unknown, excessive release of glutamate and/or other endogenous excitatory amino acid(s) which result(s) in massive influx of [Ca(+2)] into neurons (Garthwhite et al ., 1986; Choi et al ., 1987) is considered in important event. Due to the pivotal role played by polyamines in the regulation of intracellular [Ca(+2)] levels, it is likely that polyamines may have an important role in the pathophysiology of ischemic injury. Recent in vitro evidence suggests that the NMDA receptor complex has recognition sites for the polyamines, spermine and spermidine, besides the putative sites for glycine, phencyclidine (PCP), and divalent ions such as [Mg(+2)] and [Zn(+2)] (Ransom and Stec, 1988). Recently, ifenprodil, a novel NMDA receptor antagonist, was shown to interact with the polyamines (Reynolds and Miller, 1989) which may explain its unique pharmacological profile. However, the precise functional interactions of polyamines with NMDA and other excitatory amino acids are unknown at this time. The present investigation was aimed at elucidating the in vivo functional interrelationships between polyamines and the excitatory amino acids in general, and with the NMDA receptor complex in particular, by examining the effects of spermine and spermidine on mouse cerebellar cGMP levels, a well characterized excitatory amino acid receptor-mediated second messenger response (Wood et al ., 1982; 1987; 1989; Rao et al ., 1989).