Impact of intraoperative hypotension and blood pressure fluctuations on early postoperative delirium after non-cardiac surgery.

INTRODUCTION: Postoperative delirium is common in older patients. Despite its prognostic significance, the pathophysiology is incompletely understood. Although many risk factors have been identified, no reversible factors, particularly ones potentially modifiable by anaesthetic management, have been identified. The goal of this prospective cohort study was to investigate whether intraoperative hypotension was associated with postoperative delirium in older patients undergoing major non-cardiac surgery. METHODS: Study subjects were patients >65 years of age, undergoing major non-cardiac surgery, who were enrolled in an ongoing prospective observational study of the pathophysiology of postoperative delirium. Intraoperative blood pressure was measured and predefined criteria were used to define hypotension. Delirium was measured by the Confusion Assessment Method on the first two postoperative days. Data were analysed using t-tests, two-sample proportion tests and ordered logistic regression multivariable models, including correction for multiple comparisons. RESULTS: Data from 594 patients with a mean age of 73.6 years (sd 6.2) were studied. Of these 178 (30%) developed delirium on day 1 and 176 (30%) on day 2. Patients developing delirium were older, more often female, had lower preoperative cognitive scores, and underwent longer operations. Relative hypotension (decreases by 20, 30, or 40%) or absolute hypotension [mean arterial pressure (MAP)<50 mm Hg] were not significantly associated with postoperative delirium, nor was the duration of hypotension (MAP<50 mm Hg). Conversely, intraoperative blood pressure variance was significantly associated with postoperative delirium. DISCUSSION: These results showed that increased blood pressure fluctuation, not absolute or relative hypotension, was predictive of postoperative delirium.

[Lead and blood pressure]. / Piombo e pressione arteriosa.

Evidence, even if not univocal, of increase of systolic and diastolic blood pressure for Pb doses lower than 30 microg/dl stimulated studies in the last years and opened a discussion on a possible relapse in morbility and mortality, since hypertension is an important factor of cardiovascular risk. In this study, it was possible to investigate the relationship between lead and blood pressure of 303 subjects occupationally exposed to this metal with blood-Pb between 10 and 80 microg/dl and 206 subjects belonging to the general population with blood-Pb between 0.5 and 9 microg/dl. In both groups it resulted a positive and statistically significant correlation between blood-Pb values and systolic and diastolic blood pressure values, in detail in hypertensive subjects, belonging to the not-occupationally exposed group, this effect is proportionally higher. The effect of lead on blood pressure appears therefore proved, as confirmed by previous literature, but taking into consideration three specific information. It presents itself in a large range of doses, it is quantitatively very modest, it appears more evident at low doses, thus we could hypothesize different mechanisms for different doses.

[Indicators of pulmonary epithelial damage among workers at a foundry exposed to airborne pollutants]. / Indicatori di danno epiteliale polmonare in lavoratori di una acciaieria elettrica esposti ad inquinanti aerodispersi.

Foundry ambient air contains very high concentrations of noxious substances, such as particulate matter and gaseous pollutants, which can target the respiratory epithelium. Serum concentrations of the 16-kDa Clara cell protein (CC16-S) may reflect both the integrity of the epithelial barrier and smoke-induced Clara cell toxicity. To evaluate whether CC16-S is a sensitive biomarker of early respiratory disturbances, it was determined in a group of 35 foundry male workers (aged 41.1 +/- 6.9 years) examined both prior to and at the end of their work-shift (06:00 a.m.-02:00 p.m.). Exposure to inhalable/respirable dusts and PAH was characterized; urinary excretion of 1-hydroxypyrene (1-OH-P) and naphtol was measured to assess exposure to pyrene and naphthalene, respectively. CC16 serum levels decreased at the end of the shift (10.7 +/- 3.82 micrograms/L vs. 8.39 +/- 3.05 micrograms/L; p < 0.01); such decrements were significantly larger in more exposed workers. Although smokers had lower baseline values as compared to non smokers, both subgroups showed an average decrease of 30% in CC16-S concentrations at the end of shift. CC16-S was also negatively correlated with 1-OH-P, but not with naphtol concentrations. Decreased CC16-S levels can result from citotoxicity and would represent an useful biomarker of pneumotoxicity in foundry workers exposed to complex mixtures.

Cocaine and serotonin: a role for the 5-HT(1A) receptor site in the mediation of cocaine stimulant effects.

Cocaine induced locomotor stimulant effects are generally attributed to cocaine effects on brain dopamine. In this report, we present evidence that the 5-hydroxytryptamine(1A) (5-HT(1A)) agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT) and the 5-HT(1A) antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-cycylhexanecarboxaminde maleate (WAY 100635) can enhance or block, respectively, the locomotor stimulant effects induced by cocaine. In two separate experiments, rats administered cocaine (10 mg/kg) exhibited a locomotor stimulant effect and decreased grooming behavior compared to saline treated rats. Pretreatment with the 5-HT(1A) agonist, 8-OHDPAT (0.2 mg/kg) enhanced and pretreatment with the 5-HT(1A) antagonist, WAY 100635 (0.4 mg/kg) eliminated the locomotor stimulant effect of cocaine. Neither the 8-OHDPAT nor WAY 100635 effects were attributable to effects on the behavioral baseline. The 8-OHDPAT and WAY 100635 had opposite effects on grooming behavior. 8-OHDPAT decreased and WAY 100635 increased grooming. Neither treatment, however, affected the grooming suppression induced by cocaine. Ex vivo biochemical measurements indicated that neither 8-OHDPAT or WAY 100635 affected brain dopamine metabolism or cocaine availability in brain. Both treatments affected 5-HT metabolism and altered the effect of cocaine on 5-HT metabolism. 8-OHDPAT increased and WAY 100635 decreased cocaine effects on 5-HT metabolism. Cocaine and 8-OHDPAT but not WAY 100635 increased corticosterone. Altogether, these findings indicate that the 5-HT(1A) receptor site may be an important target for the development of pharmacotherapies for the treatment of cocaine abuse.

The 5-HT(1A) antagonist WAY 100635 can block the low-dose locomotor stimulant effects of cocaine.

Cocaine treatments of 2.5, 5.0, 10.0 and 15.0 mg/kg induced dose-dependent increases in locomotor behavior. This cocaine-induced increase in locomotion was blocked if the animals were administered the selective 5-HT(1A) antagonist, WAY 100635 (0.4 mg/kg) prior to the cocaine treatment. The 0.4-mg/kg dose of WAY 100635 did not affect locomotor behavior or alter cocaine availability in brain.

Large-scale cDNA analysis reveals phased gene expression patterns during preimplantation mouse development.

Little is known about gene action in the preimplantation events that initiate mammalian development. Based on cDNA collections made from each stage from egg to blastocyst, 25438 3'-ESTs were derived, and represent 9718 genes, half of them novel. Thus, a considerable fraction of mammalian genes is dedicated to embryonic expression. This study reveals profound changes in gene expression that include the transient induction of transcripts at each stage. These results raise the possibility that development is driven by the action of a series of stage-specific expressed genes. The new genes, 798 of them placed on the mouse genetic map, provide entry points for analyses of human and mouse developmental disorders.

Issues in the pharmacological modification of cocaine conditioning: evidence that the stimulus properties of drugs can interact with contextual cues to activate or inactivate cocaine conditioned stimuli.

Cocaine conditioned stimuli are capable of eliciting cocaine craving in individuals with a history of cocaine use. As a consequence, there have been a number of attempts using animal models to identify pharmacological treatments which can attenuate cocaine conditioned effects. The emphasis in these studies has been to employ drug doses which do not have response effects that could directly alter the conditioned drug response. A drug treatment may not have a response effect but still have drug stimulus effects which could interact with and modify the cocaine conditioned stimulus. In order to experimentally investigate this important issue, two experiments are reported. In one experiment, rats were co-administered 0.1 mg/kg MK-801 either with cocaine (10 mg/kg) or with saline; in the other experiment 3.0 mg/kg buspirone was co-administered with either cocaine (10 mg/kg) or with saline. The MK-801 and buspirone treatments did not affect spontaneous activity levels or alter the unconditioned cocaine stimulant effect. In tests for conditioning, however, the effects of buspirone and MK-801 depended upon their association with cocaine. If MK-801 and buspirone had no association with cocaine then these drugs inactivated the cocaine conditioned stimulant response. If MK-801 and buspirone had been co-administered with cocaine, then, in saline conditioning tests, no cocaine conditioning was observed. If the conditioning tests were conducted following MK-801 or buspirone treatment, however, cocaine conditioning was elicited. Altogether, these studies demonstrate that the stimulus properties of drugs can interact with contextual stimuli to inactivate or activate cocaine conditioned stimuli. In the search for drugs which may prevent cocaine craving, therefore, the stimulus properties of drugs provide an important mechanism for the modification of cocaine conditioned stimuli.

A simple, rapid HPLC method for the concurrent measurement of cocaine and catecholamines in brain tissue samples.

We describe a simplified HPLC method for the measurement of cocaine and catecholamines in the same brain tissue sample. Using this method to measure cocaine in the brain of rats which received either 10 or 20 mg/kg cocaine injections, we found substantial cocaine concentration differences between medial prefrontal cortex, striatum and limbic brain areas. Specifically, for each cocaine dose level there was a nearly 2-fold differential between cocaine concentration in the cortex as compared to limbic tissue. A shortcoming of many neurobehavioral studies of cocaine effects is the absence of brain cocaine measurements. The simplicity of the present method makes the measurement of cocaine and catecholamines from the same tissue sample a procedure which can readily be incorporated in the studies designed to evaluate the neurochemical effects of cocaine treatments.

A simplified method for the measurement of caffeine in plasma and brain: evidence for a cortical-subcortical caffeine concentration differential in brain.

We describe a much simplified high-performance liquid chromatography (HPLC) method for the measurement of caffeine in plasma and brain. A particularly attractive feature of this method is that a simple methanol/water (60:40) mobile phase can be used both for plasma and brain samples. In addition, the method is compatible with solid-phase extraction for plasma samples and conventional brain tissue preparation for biogenic amine analysis with HPLC. Using this method to measure the concentrations of caffeine in plasma and brain of rats which received 10 or 50 mg/kg caffeine injections, we found substantial concentration differences between cortical and subcortical brain tissue. Specifically, at the 10 mg/kg dose, a nearly 2-fold difference between cortex and striatum caffeine concentrations was observed. A shortcoming of many neurobehavioral studies of caffeine effects is the absence of caffeine concentration measurements. The simplicity of the present method for the measurement of caffeine in plasma and brain tissue makes it a practical and feasible procedure to incorporate into neurobehavioral studies designed to elucidate the CNS actions of caffeine.

Differential temporal dynamics of serum and brain cocaine: relationship to behavioral, neuroendocrine and neurochemical cocaine induced responses.

Rats administered cocaine 10 mg/kg i.p. exhibited hyperlocomotion which occurred within 5 min post injection. Subsequently, rats were injected with 10 mg/kg cocaine and brain and serum concentrations of cocaine were measured at 5, 10, and 20 min post injection. Within this time frame, cocaine concentration in limbic brain tissue was maximal at 5 min post injection and then declined substantially by 20 min post injection. In contrast, serum cocaine concentration increased from 5 to 20 min post injection. Neurochemical effects of cocaine upon limbic dopamine turnover and plasma corticosterone had a time course similar to serum cocaine. Brain cocaine concentrations paralleled the locomotor stimulant cocaine response whereas cocaine neuroendocrine effects paralleled serum cocaine concentrations. These findings point to the importance of brain cocaine concentration determinations in neurobehavioral studies of cocaine.