Inhibition of the histamine-induced Ca2+ influx in primary human endothelial cells (HUVEC) by volatile anaesthetics.

BACKGROUND AND OBJECTIVE: Vasoactive substances such as histamine, acetylcholine or ATP increase the [Ca2+]i of endothelial cells, which leads to the activation of nitric oxide synthase (eNOS). The NO produced by this enzyme relaxes the underlying smooth muscle. Evidence suggests that eNOS activation is dependent on agonist-induced Ca2+ entry. Recently we have shown that in human endothelial cells (HUVEC), this Ca2+ entry is sensitive to isoflurane. The objective here was to study the mechanism by which volatile anaesthetics can depress the histamine-induced Ca2+ entry into HUVEC cells. METHODS: HUVECs on coverslips were loaded with the Ca2+ indicator Fluo-3 and inserted in a gastight, temperature-controlled perfusion chamber. Excitation was at 488 nm and fluorescence signals were monitored with a confocal laser scanning microscope (MRC1024, Biorad). Direct measurement of the Ca2+ influx was with Mn2+ as surrogate for calcium at 360 nm in cells loaded with Fura-2. RESULTS: Addition of histamine induces a biphasic [Ca2+]i increase consisting of Ca2+ release from internal stores and a Ca2+ influx from the external medium (plateau phase). The plateau phase was dose-dependently inhibited by enflurane and sevoflurane (13.7 resp. 21.9% inhibition by 1 MAC anaesthetic). Direct measurement of the Ca2+ influx using the Mn2+ quench of the Fura-2 fluorescence gave similar results. The inhibition of the anaesthetics was not reduced by inhibition of the cGMP pathway, inactivation of protein kinase C, depolarization of the cells or the presence of specific Ca2+-dependent K+ channel inhibitors. Interestingly, unsaturated fatty acids inhibit the histamine-induced Ca2+ influx in a similar way as the volatile anaesthetics. CONCLUSIONS: Volatile anaesthetics dose-dependently inhibit the histamine-induced Ca2+ influx in HUVECs by a mechanism that may involve unspecific perturbation of the lipid bilayer.

Taste in dementing diseases and parkinsonism.

Like with many sensory abilities a reduction of taste and smell occurs during aging. Since there are hints to an additional reduction in dementing diseases, we assessed 52 patients, 26 women and 26 men, who were presented to a memory clinic, using the Sniffin' Sticks, Whole Mouth and Taste Strip Tests. While smoking, alcohol consumption, intake of drugs and sex exerted only minor impact, age and the severity of cognitive impairment were of major importance. There was a moderate but significant correlation between the severity of dementia, taste and smell, even if the age effect was partialled out. Notably, patients with Parkinson syndrome showed worse taste and smell abilities than those without. Here the differences were indeed marked enough to play a possible role in making the diagnosis. This exploratory study confirms a mild reduction of gustatory function in dementing diseases over and beyond that of normal aging which--in addition to a reduction of smell--seems to be especially marked in Parkinson syndromes.

The Kent hip prosthesis: an evaluation of 145 prostheses after a mean of 5.1 years.

The Kent hip is a distally-locked femoral stem which was developed to address severe proximal bone loss, severe bony deformity and peri-prosthetic fracture. We reviewed the results of 145 consecutive Kent hips implanted into 141 patients between 1987 and 2000. The indications for implantation were aseptic loosening (75 hips), septic loosening (two), peri-prosthetic and prosthetic fracture (37), severe bony deformity (24), and fracture through a proximal femoral metastasis (seven). The median time to full weight-bearing after surgery was two days and the mean length of follow-up was 5.1 years (2 to 15). Further revisions were required for 13 femoral stems. With removal of the stem for any reason as an end-point, the cumulative survival at five, ten and 15 years was 93%, 89% and 77%, respectively. In patients aged>or=70 years, the cumulative survival at 15 years was 92%, compared with 68% in those aged<70 years. Because of these findings, we recommend the use of interlocking stems in patients aged>or=70 years, particularly in those with a peri-prosthetic fracture, for whom alternative methods are limited. Outcome scores and survival data, compared with other systems, indicate that the Kent hip should be used with caution in younger patients.

Social determinants of experienced anger.

We investigated two social determinants (i.e., availability of social support and status differentials of the provocateur) for the degree of perceived anger in two populations. Because no suitable tool was available, the conceptual and psychometric development and validation of a new vignette-based measure for anger level (STandardized Experience of Anger Measure, STEAM) is described first. Two versions of STEAM were developed: one for students and one for community-living adults. Through a series of four studies, two sets of a 12-item vignette-based questionnaire were developed and validated. The resulting test had excellent test-retest stability and high internal consistency. Using the new STEAM measure, a variety of analyses were conducted to test the hypothesized influence of social determinants of anger. In the student sample, presence of social support was associated with lessened anger, and in both samples decreasing status of the provocateur also led to lessened anger arousal. In addition, findings in both samples revealed that social support reduced anger when the provocateur was of higher status relative to situations of equal and lesser status. In the community sample, the availability of support was associated with greater intensity of the anger experience in the lesser status condition than in the equal or greater status condition. No gender main effects or interactions were noted.

Alexithymia, defensiveness and cardiovascular reactivity to stress.

This article attempts to further our understanding of alexithymia by testing two conceptual questions about the construct: (a) Is alexithymia characterized by reduced autonomic activity? and (b) Can it be clearly distinguished from defensiveness? Eighty healthy university students completed a battery of personality scales including the Toronto Alexithymia Scale, measures of self-deception and impression management, depression, and anger-in. They also participated in three lab stress tasks: isometric handgrip; mental arithmetic; and a negative affect provocation task. Blood pressure and heart rate were monitored throughout the lab procedure. Analyses were conducted with tercile groups of low, medium, and high alexithymia scorers. The "high alexithymia" tercile showed smaller heart rate responses to the stress tasks and more anger-in behavior. Blood pressure responses did not differentiate the low/ medium/high alexithymia subgroups. Alexithymia scores were unrelated to defensiveness, that is, there was no relationship between alexithymia and impression management or self-deception, and alexithymia was unrelated to depression. We conclude that students defined as "high alexithymia" on the Toronto Alexithymia Scale are not self-deceptive nor do they try to leave a particular impression; they tend to be somewhat hypoaroused autonomically, and they report as many psychological distress symptoms as do subjects with lower TAS scores.

Psychosocial interventions for patients with coronary artery disease: a meta-analysis.

BACKGROUND: Narrative review strategies and meta-analyses have shown that drug treatment and exercise rehabilitation regimens can reduce psychological distress and postmyocardial infarction mortality and recurrence. OBJECTIVE: To question whether the addition of psychosocial interventions improves the outcome of a standard rehabilitation regimen for patients with coronary artery disease. METHODS: We performed a statistical meta-analysis of 23 randomized controlled trials that evaluated the additional impact of psychosocial treatment of rehabilitation from documented coronary artery disease. Anxiety, depression, biological risk factors, mortality, and recurrence of cardiac events were the clinical end points that were studied. Mortality data were available from 12 studies, and recurrence data were available from 10 of the 23 studies. RESULTS: The studies had evaluated 2024 patients who received psychosocial treatment vs 1156 control subjects. The psychosocially treated patients showed greater reductions in psychological distress, systolic blood pressure, heart rate, and cholesterol level (with effect size differences of -0.34 [corrected], -0.24, -0.38, and -1.54, respectively). Patients who did not receive psychosocial treatment showed greater mortality and cardiac recurrence rates during the first 2 years of follow-up with log-adjusted odds ratios of 1.70 for mortality (95% confidence interval [CI], 1.09 to 2.64) and 1.84 for recurrence (CI, 1.12 to 2.99). CONCLUSIONS: The addition of psychosocial treatments to standard cardiac rehabilitation regimens reduces mortality and morbidity, psychological distress, and some biological risk factors. The benefits were clearly evident during the first 2 years and were weaker thereafter. At the clinical level, it is recommended to include routinely psychosocial treatment components in cardiac rehabilitation. The findings also suggest an urgent need to identify the specific, most effective types of psychosocial interventions via controlled research.