Increased GABAergic transmission aggravates nucleus basalis magnocellularis lesion-induced behavioral deficits

Quisqualic acid NBM lesions had no effect on water maze performance, but slightly impaired passive avoidance acquisition. GammavinylGABA treatment alone had no effect on the passive avoidance and water maze performance, but aggravated acquisition deficit in rats subjected to NBM lesioning. However, gammavinylGABA-treated NBM-lesioned rats reached control level of performance.     

Evaluation and Treatment of Depression in Managed Care (Part II)

Depression is under-detected, but is treatable and relapses can be prevented. Living with depression, whether acute or chronic, has consequences for quality of life, premature end of life, and productive life. Thoughtful and strategic quality improvement (QI) programs offer one avenue for improving the treatment of depression. Part I of this two-part series addresses improving the treatment of depression and employing disease management as a strategy to accomplish that aim. This article, part II, provides an overview of other QI initiatives that demonstrated treatment effectiveness for depression, including several used in managed care practice.Currently, the majority of QI programs for depression target adult patients; therefore, there are future challenges ahead as managed care attempts to address the needs of special populations, such as adolescents and older adults. Public education, professional education, and population-based interventions are also considerations as part of successful treatment. Although consumer-based interventions are typically more expensive, they may ultimately yield the best results for improving depression care for the consumer and payors based on available research. The success of a consumer-centric approach is highly reliant on the person’s engagement with QI programs, the treating clinician’s appreciation and support of such depression programs, and managed care’s response to solving quality problems using continuous monitoring, evaluation, feedback, system enhancements, and training. Models of collaboration between consumers and medical and behavioral health systems offer the most promising approaches to care improvements for patients with depression.     

Postoperative Cognitive Dysfunction in Middle-aged Patients

Background: Postoperative cognitive dysfunction (POCD) after noncardiac surgery is strongly associated with increasing age in elderly patients; middle-aged patients (aged 40-60 yr) may be expected to have a lower incidence, although subjective complaints are frequent.

Methods: The authors compared the changes in neuropsychological test results at 1 week and 3 months in patients aged 40-60 yr, using a battery of neuropsychological tests, with those of age-matched control subjects using Z-score analysis. They assessed risk factors and associations of POCD with measures of subjective cognitive function, depression, and activities of daily living.

Results: At 7 days, cognitive dysfunction as defined was present in 19.2% (confidence interval [CI], 15.7-23.1) of the patients and in 4.0% (CI, 1.6-8.0) of control subjects (P < 0.001). After 3 months, the incidence was 6.2% (CI, 4.1-8.9) in patients and 4.1% (CI, 1.7-8.4) in control subjects (not significant). POCD at 7 days was associated with supplementary epidural analgesia and reported avoidance of alcohol consumption. At 3 months, 29% of patients had subjective symptoms of POCD, and this finding was associated with depression. Early POCD was associated with reports of lower activity scores at 3 months.     

High affinity neurotrophin receptors in the human pre-term newborn, infant, and adult cerebellum

The immunohistochemical occurrence of the high affinity neurotrophin (NT) receptors trkA, trkB, and trkC is shown in the pre-term newborn, infant, and adult human post-mortem cerebellum. Immunoreactive neuronal perikarya and processes were observed in all specimens examined, where they appeared unevenly distributed in the cerebellar cortical layers and deep nuclei, and showed regional differences among cerebellar lobules and folia. The trk receptor-antibodies, tested by Western blot on human cerebellum homogenates, revealed multiple immunoreactive bands for trkA and single bands for trkB and trkC. The results obtained show the tissue localization of the trk receptor-like immunoreactivity in the human cerebellum from prenatal to adult age. The analysis for codistribution of the receptors with the relevant ligand and among the receptors in discrete cortical and deep nuclei tissue fields shows a wide variety of conditions, from a good similarity in terms of type and density of labeled structures, to a lack of correspondence, and suggests the possibility of colocalization of trk receptors with the relevant neurotrophin and among them in the cerebellar cortex. These results sustain the concept that the neurotrophin trophic system participates in the development, differentiation, and maintenance of the human cerebellar connectivity and support the possibility of a multifactorial trophic support for the neurotrophins through target-derived and local mechanisms.     

Intrinsic resistance to anticancer agents in the murine pancreatic adenocarcinoma PANC02

Summary PANC02 is a ductal adenocarcinoma of the pancreas that is resistant to every known class of clinically active antitumor agent. To study the mechanism(s) underlying the intrinsic drug resistance of this tumor, a mammary adenocarcinoma (CA-755) that also grows in C57/BL mice and is known to be drugsensitive was used for comparison. PANC02 resistance and CA-755 sensitivity to several antitumor agents and to X-ray therapy was confirmed in mice, and PANC02 also demonstrated relative resistance in tissue culture. Relative to Chinese hamster ovary (CHO) and CA-755 cells, PANC02 did not appear to show a higher rate of mutation to drug resistance in culture as based on the 6-thioguanine resistance marker. Although P-glycoprotein characteristic of the multidrug resistance (MDR) phenomenon could be demonstrated at the mRNA level using a sensitive RNAse protection assay, the level of expression found was several orders of magnitude lower than that observed in phenotypic MDR cell lines. Furthermore, quinidine failed to increase the sensitivity of PANC02 cells to Adriamycin under conditions that clearly potentiated the toxicity of the drug to a CHO cell line exhibiting classic MDR traits. The heterogeneity in the distribution of drugs was inferred as being significantly greater in PANC02 versus CA-755 cells in vivo as based on measurements of within-animal, within-tumor variance in the distribution of the marker compounds inulin and antipyrine. Although it may not be the only mechanism involved, this greater intratumor heterogeneity in drug distribution could theoretically play a major role in the intrinsic drug resistance of PANC02 in vivo.Supported by grant CH-458 from the American Cancer Society, by grant CA-28034 from the National Cancer Institute, and in part by Cancer Center Core Support grant, NIH-NCI-CA-16672. Animals were maintained in facilities approved by the American Association for Accreditation of Laboratory Animal Care and in accordance with current United States Department of Agriculture, Department of Health and Human Services, and National Institutes of Health regulations and standards     

High Stroke Volume Para-aortic Counterpulsation Device versus Centrifugal Pump in Cardiogenic Shock: Experimental Study

p < 0.001), the tension time index (712 ± 381 versus 1333 ± 694, p < 0.01), and the double product (5629 ± 2574 versus 7440 ± 3294, p < 0.01) were significantly lower during assistance with the PACD than with the CBP. It was concluded that PACD is at least as effective as CBP for restoring hemodynamic status during acute experimental cardiogenic shock. Moreover, the PACD unloads the left ventricle more effectively than CBP, making it suitable for left ventricular mechanical support in cases with reversible myocardial damage.     

Dolichol content in isolated sinusoidal liver cells after in vivo chronic treatment with thioacetamide.

The content of dolichol, an isoprenoid present in all biological membranes, was determined in isolated sinusoidal liver cells after treatment of rats for 2 and 4 months with a low dosage of the hepatotoxin thioacetamide. The significant decrease in dolichol observed in hepatocytes after 2 months might be explained by peroxidation of the isoprenoid. At the same time point, retinol was retained, and decreased only after 4 months of treatment. After 4 months of treatment therefore both lipids decreased. In a subfraction of hepatic stellate cells, Ito-1 cells, the main storage site of vitamin A, dolichol decreased significantly only after 4 months. A remarkable difference from hepatocytes is that in Ito-1 cells retinol content significantly decreased after 2 months of treatment. In another subfraction, Ito-2 cells, the content of the two isoprenoids decreased in parallel. This heterogeneous subfraction might represent those transitional hepatic stellate cells that, while losing retinol, are in the process of differentiating into myofibroblasts secreting extracellular matrix components. In Kupffer cells and sinusoidal endothelial cells, impairment of dolichol might be observed later, only after 4 months of treatment, while retinol decreases uniformly over time. Starting after two months of treatment, the decrease of dolichol and the increase of retinol in hepatocytes, at the same time as retinol decreases in hepatic stellate cells, might be taken as an early index of incipient liver injury due to thioacetamide. This hypothesis is discussed with regard to a role of dolichol in the modulation of membrane fluidity for intracellular and intercellular retinol transport.     

Effect of artifacts due to flowing blood on the reproducibility of phase-contrast measurements of myocardial motion

The reproducibility of myocardial motion trajectories calculated from cine phase-contrast (PC) velocity data is reduced by artifacts due to the inconsistent motion of intracardiac blood. Spatial presaturation reduces these artifacts but requires a longer sequence TR, with a potentially negative effect on trajectory accuracy and reproducibility. We investigated the effect of spatial presaturation on trajectory reproducibility. A midventricular transaxial slice was imaged in five normal volunteers. The same slice was imaged three times each with sequences using spatial presaturation or not. Because the most serious artifacts originate in the heart chambers and propagate in the phase-encoded direction, myocardial regions that were in line with the heart chambers (in the phase-encode direction) had the highest artifact level in the scans without spatial presaturation. The reproducibility of trajectories for regions placed in these areas (the anterior wall, septum and posterior wall in the transaxial scans with phase encoding in the anterior-posterior direction) improved by a factor of two when presaturation was used (P < .001). In areas that were not in line with the heart chambers (eg, the anterior aspect of the lateral wall in the transaxial scans), the effect of presaturation was not significant. These results correlate well with the measured reduction in artifact level. The reproducibility of myocardial motion trajectories over large areas of the heart is improved to approximately 1 mm when presaturation is used. Therefore, use of presaturation is recommended for myocardial motion studies using cine PC velocity data.     

Chromosomes in Anorexia Nervosa. A Study of 47 Cases Including a Population-Based Group: A Research Note

Forty-seven cases with anorexia nervosa (including a total population group) and 47 sex-, age-, and school-matched comparison cases were subjected to chromosome analyses in a blind fashion. No major abnormalities were found in any of the cases. Sex chromatin was analysed in buccal smears from the girls. No differences between the anorexia nervosa and the comparison cases were found. It seems that chromosomal/sex chromatin analyses in anorexia nervosa are not warranted.     

Immediate saccade amplitude disconjugacy induced by unequal images

We tested the ability of normal subjects to make changes in the conjugacy of their saccades. Subjects dichoptically viewed a grid the size of which was 10% larger in one eye. The grids were centred onto a flat screen at 57 cm or 1 m from the subject. Horizontal saccades immediately became larger in the eye viewing the larger grid. For some subjects this disconjugacy persisted even under subsequent monocular viewing. Such persistent changes occurred mainly in the field where the required disconjugacy was divergent for centrifugal saccades, convergent for centripetal saccades. Vertical saccades also developed compensatory disconjugacy; its amplitude was smaller but less variable. To explain these results we propose a fast associative learning mechanism that pairs peripheral disparity with saccades and is capable of producing saccade disconjugacy even in the absence of disparity. For horizontal saccades a secondary conditioning of monocular depth cues by the disparity would also be involved.