Pupillary responses to intranasal trigeminal and olfactory stimulation

The aim of the present study was to investigate whether pupillary responses to odorous stimuli reflect their intensity or hedonic tone. A total of 21 healthy subjects participated in the study. Using a computer-controlled olfactometer, subjects received intranasal stimuli including odors of rose (PEA; 2 concentrations), lemon and rotten eggs, plus the trigeminal irritant CO₂ (also at two concentrations). Changes in the pupil diameter were obtained ipsilaterally to the side of stimulus presentation. Both trigeminal and olfactory stimulation produced an increase in pupillary diameter. Latencies for pupillary reaction were fastest for the higher concentration of CO₂ and slowest after the presentation of PEA at the low concentration. Response amplitudes were largest in response to stimulation with CO₂ at the high concentration, while they were smallest in response to odorous stimulation with PEA. Response latencies decreased with increasing stimulus intensity. No such correlation was found for hedonic ratings and pupillary reactions. Thus, the change in the pupillary diameter indicates differences between stimulus modalities and stimulus strength, but not pleasantness or unpleasantness of the odors.     

Carbon dioxide suppresses macrophage superoxide anion production independent of extracellular pH and mitochondrial activity

Background

Superoxide anions released by activated macrophages during surgery are considered to be responsible for local cellular damage. Application of CO₂ pneumoperitoneum during laparoscopy affects superoxide anion release, but the underlying mechanism remains unclear and the data reported are conflicting. We investigated the direct and pH-mediated impact of CO₂ and air on macrophage superoxide anion production.

Methods

Cells of the NR 8383 rat macrophage cell line were incubated for 2 hours in 5% CO₂, 100% CO₂, and room air or pH 7.4, pH 6.5, and pH 5.5. The extracellular pH was monitored during incubation. At 0, 2, and 6 hours after incubation, the release of superoxide anions was determined fluorometrically. The mitochondrial activity was determined via the conversion of MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] during and after incubation.

Results

Extracellular pH decreased to 6.4 during incubation in a CO₂ atmosphere. The release of superoxide anions was significantly reduced immediately after CO₂ incubation. It was restored at all other time-points. Decreasing the extracellular pH to 6.5 had no effect on superoxide anion release, whereas acidification of the extracellular milieu to pH 5.5 significantly suppressed subsequent superoxide release. Mitochondrial activity was significantly decreased by CO₂ up to 2 hours and by acidic milieu up to 6 hours. Incubation in room air had no effect.

Conclusions

Incubation in CO₂ can directly suppress macrophage superoxide anion production. This effect is of short duration, fully reversible, and not correlated to changes in extracellular pH or mitochondrial activity. Air contamination does not affect macrophage superoxide anion release. We speculate that CO₂ pneumoperitoneum could attenuate the intraoperative free radical production by directly inhibiting superoxide anion release of macrophages without long-lasting suppression of macrophages and their capacity to release superoxide anions postoperatively.     

Cost-Effectiveness of Acupuncture in Women and Men With Allergic Rhinitis: A Randomized Controlled Study in Usual Care

To assess quality of life and cost-effectiveness of additionalacupuncture treatment for allergic rhinitis, patients were randomlyallocated to 2 groups; both received usual care, but one groupreceived an additional 10 acupuncture sessions. Quality of life(according to the SF-36 Health Survey), and direct and indirectcosts, were assessed at baseline and after 3 months, and theincremental cost-effectiveness ratio of acupuncture treatmentwas calculated. This German study (December 2000–June2004) involved 981 patients (64% women, mean age 40.9 years(standard deviation, 11.2); 36% men, mean age 43.2 years (standarddeviation, 13.0)). At 3 months, quality of life was higher inthe acupuncture group than in the control group (mean PhysicalComponent Score 51.99 (standard error (SE), 0.33) vs. 48.25(SE, 0.33), P < 0.001; mean Mental Component Score 48.55(SE, 0.42) vs. 45.35 (SE, 0.42), respectively, P < 0.001).Overall costs in the acupuncture group were significantly higherthan those in the control group (Euro (; 1 = US $1.27)763, 95%confidence interval: 683, 844 vs. 332, 95% confidence interval:252, 412; mean difference 432, 95% confidence interval: 318,545). The incremental cost-effectiveness ratio was 17,377 perquality-adjusted life year (women, 10,155; men, 44,871) andwas robust in sensitivity analyses. Acupuncture, supplementaryto routine care, was beneficial and, according to internationalbenchmarks, cost-effective. However, because of the study design,it remains unclear whether the effects are acupuncture specific. acupuncture; cost-benefit analysis; economics; quality of life; rhinitis, allergic, perennial; rhinitis, allergic, seasonal     

Patterns of physician and patient rated quality of life during antipsychotic treatment in outpatients with schizophrenia

Quality of life (QoL) in patients with schizophrenia has been assessed both from physician and patient perspectives, but little is known about agreement between these perspectives and predictors of agreement. The aim of this study was to analyze a large sample of patients with schizophrenia to discover patterns of physician and patient-rated QoL in patients with schizophrenia and identify predictors for these patterns. This study (EASE) was designed to investigate the QoL and subjective well-being in out-patients with schizophrenia during antipsychotic treatment in a naturalistic setting. Assessments were carried out at baseline and at 3, 6, 9 and 12 months, using the quality of life scale (QLS) and the subjective well-being on neuroleptics scale (SWN-K). A hierarchical cluster analysis was used to define groups of patients based on the SWN-K and QLS total scores at all visits. 1174 patients were included in the cluster analyses that were based on SWN-K and QLS total scores over time. Four distinct clusters were identified: patients with: (1) continuously high QoL (23.2%), (2) continuously moderate QoL (45.8%), (3) continuously low QoL (11.2%), and (4) improving QoL (19.9%). Clusters 1-3 were stable in terms of QoL, whilst cluster 4 changed towards improvement. Various predictors for the four clusters were identified. In the cluster with improving QoL, the absence of treatment with an oral conventional antipsychotic pre-study and no medication change due to lack of efficacy at baseline were predictors for improvement. In the cluster with continuously high QoL, no medication change due to lack of efficacy and lowest CGI-S scores at baseline were predictors. Oral conventional antipsychotic treatment pre-study was predictive for the cluster with continuously moderate QoL. In the cluster with continuously low QoL, medication change due to lack of efficacy and highest CGI-S scores were predictors. These findings suggest that various factors may predict whether a patient with schizophrenia experiences a continuously high QoL, a continuously moderate QoL, a continuously low QoL, or improving QoL whilst on antipsychotic treatment.     

Subcortical contributions to multitasking and response inhibition

The involvement of the prefrontal cortex in executive control has been well established. It is, however, as yet unclear whether the basal ganglia and the cerebellum as components of frontostriatal/frontocerebellar networks also contribute to the executive domains multitasking and response inhibition. To investigate this issue, groups of patients with selective vascular lesions of the basal ganglia (n=13) or the cerebellum (n=14) were compared with matched healthy control groups. Several paradigms assessing the ability to process concurrent visual and auditory input and to simultaneously perform verbal and manual responses as well as the inhibition of habitual or newly acquired response tendencies were administered. Basal ganglia patients showed marked response slowing during coordination of sensory input from different modalities and high error rates during the inhibition of overlearned responses. There was no clear evidence of a cerebellar involvement in multitasking or response suppression. Taken together, the findings provided evidence for a striatal involvement in both multitasking and response inhibition, emphasizing the functional implication of subcortical components in frontostriatal circuits.     

Genome-wide expression patterns of invasion front, inner tumor mass and surrounding normal epithelium of colorectal tumors

Background

The normal human prostate glandular epithelium has the unique function of accumulating high levels of zinc. In prostate cancer this capability is lost as an early event in the development of the malignant cells. The mechanism and factors responsible for the ability of the normal epithelial cells to accumulate zinc and the loss of this capability in the malignant cells need to be identified. We previously reported that Zip1 is an important zinc uptake transporter in prostate cells and is down regulated in the malignant cells in situ along with the depletion of zinc levels. In this report we investigated the expression of two other Zip family zinc transporters, Zip2 and Zip3 in malignant versus nonmalignant (normal and BPH) glands. Zip2 and Zip3 relative protein levels were determined by immunohistochemistry analysis of human prostate tissue sections.

Results

Normal and BPH glandular epithelium consistently exhibited the strong presence of both Zip 2 and Zip3; whereas both transporters consistently were essentially non-detectable in the malignant glands. This represents the first report of the expression of Zip3 in human prostate tissue; and more importantly, reveals that ZiP2 and Zip3 are down regulated in malignant cells in situ as we also had demonstrated for Zip1. Zip2 and Zip3 transporter proteins were localized predominantly at the apical cell membrane, which is in contrast to the Zip1 localization at the basolateral membrane. Zip2 and Zip3 seemingly are associated with the re-uptake of zinc from prostatic fluid.

Conclusion

These results coupled with previous reports implicate Zip2 and Zip3 along with Zip1 as important zinc uptake transporters involved in the unique ability of prostate cells to accumulate high cellular zinc levels. Zip1 is important for the extraction of zinc from circulation as the primary source of cellular zinc. Zip 2 and Zip3 appear to be important for retention of the zinc in the cellular compartment. The down regulation of all three transporters in the malignant cells is consistent with the loss of zinc accumulation in these cells. Since zinc imposes tumor suppressor effects, the silencing of the gene expression for these transporters is a required event for the manifestation of the malignant activities of the neoplastic cells. This now provides new insights into the genetic/molecular events associated with the development of prostate cancer; and supports our concept of Zip1, and now Zip2 and Zip3, as tumor suppressor genes and zinc as a tumor suppressor agent.     

Huntington disease: a case study of early onset presenting as depression

Huntington disease is a dominantly inherited, neurodegenerative disease characterized by choreiform movement disturbances and dementia, usually with adult onset. The rare juvenile-onset Huntington disease differs from the adult phenotype. A case presenting twice, at age 10 with all the signs of a major depression and age 14 with mutism and rigidity, is reported. Meanwhile, the father developed the adult variant of Huntington disease. The boy's diagnosis was confirmed by molecular genetic analysis and magnetic resonance imaging. It is important to be aware of hereditary conditions such as Huntington disease and to provide family counseling before genetic testing and after the diagnosis is confirmed.