The effect of repeated isoflurane anesthesia on spatial and psychomotor performance in young and aged mice

Exposure to general anesthesia may contribute to postoperative cognitive impairment in elderly patients, but the relationship remains poorly understood. We investigated whether aged mice, 18-19 mo, are more susceptible to postanesthetic cognitive impairment than young mice, 3-4 mo, using spatial memory (Barnes maze) and psychomotor (rotarod) tasks. Initially we studied the effect of a single anesthetic episode on asymptotic maze performance. We then tested whether repeated anesthesia would impair spatial memory and psychomotor performance to a greater extent in aged mice. Mice were anesthetized with isoflurane (1.4% atm) for 30 min; controls received 90% oxygen. Anesthesia, administered during the asymptotic period of maze learning, did not impair performance tested the following day (P > 0.05). Repeated anesthesia, 2-3 h after each session, did not impair overall maze or rotarod performance in young or aged mice (P > 0.05). Spatial learning appeared to be facilitated by anesthesia, F(1,204) = 7.97, P < 0.01 for pooled results. Asymptotic performance-when learning had stabilized-remained unimpaired in both the maze and rotarod tasks. These results suggest that an age-related risk of anesthetic-induced impairment appears to be limited to acquisition of a novel motor skill and that anesthesia alone does not lead to prolonged cognitive impairments in aged mice. IMPLICATIONS: This study demonstrates that repeated isoflurane general anesthesia impaired psychomotor performance in aged mice during the initial learning period; however, spatial learning improved and, overall, spatial memory and psychomotor performance were unimpaired. Thus, general anesthesia alone does not appear to result in prolonged cognitive deficits in aged mice.     

Cyclin S: a new member of the cyclin family plays a role in long-term memory

Memory is thought to be subserved by structural and functional alteration in synaptic connectivity. But although neuronal plasticity requires gene expression, the identity of the proteins involved is largely unknown. Using the chick 1-day-old passive avoidance learning paradigm and differential display RNA fingerprinting, we identified 13 candidate genes which are upregulated in the intermediate medial hyperstriatum ventrale (IMHV), an area that has been correlated with the initial processing of memory formation. One of the induced genes is a new member of the cyclin family, with high homology to cyclin L (ania-6a). Analysis of the expression pattern of this gene after training revealed two time waves of induction: the first correlated with learning and initial memory process in the IMHV; the second correlated with memory consolidation, first in the IMHV, and then in the lobus paraolefactoris. There is a correlation between methylanthranilate (MeA) concentrations (the malaise substrate in the passive avoidance training procedure), the duration of memory and the expression level of cyclin S. While training chicks on low concentrations of MeA causes short-term memory and low expression level of cyclin S, high concentration of MeA induces long-term memory and high expression level of cyclin S in the IMHV. The role of cyclins in the regulation of neuronal-plasticity-related gene expression was overlooked, and it might serve as a key step in long-term memory formation.     

The KickStrip: a novel testing device for periodic limb movement disorder

STUDY OBJECTIVES: In light of the ongoing debate over the clinical significance of periodic limb movement disorder (PLMD) and its monitoring in overnight sleep studies, we introduce a novel, portable, low-cost device for PLMD testing. The KickStrip is a disposable device, which includes a movement sensor, a central processing unit with real-time software, and a display. In the present study, the KickStrip final score (Kscore) is validated against the traditional periodic limb movement index (PLMI) based on overnight recordings in the sleep laboratory. DEISGN: Patients underwent full polysomnographic recordings concomitantly with the use of the KickStrip for a single night. SETTING: Sleep Disorders Unit at Loewenstein Rehabilitation Hospital and Sleep Medicine Center at Rambam Medical Center, Israel. PATIENTS: Eighty-two patients referred for overnight sleep recordings due to sleep disturbance of any kind. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The Kscores were collected and the PLMI computed for each leg separately. Pearson correlations between Kscores and PLMI ranged between r = 0.83 to r = 0.88 (p < 0.001). Sensitivity and specificity values of the Kscores for increasing PLMD thresholds showed sensitivity ranging from 50% to 100% and specificity ranging from 83% to 100%. Receiver operating characteristic curves showed area-under-the-curve values ranging from 82% to 92%. Bland-Altman plot showed high agreement between the methods. CONCLUSIONS: Comparisons between the Kscores and the traditional PLMI show increased accuracy with severity level and excellent agreement. The KickStrip is a valuable tool for PLMD testing for both clinical and research purposes.     

New syndrome of simplified gyral pattern,micromelia, dysmorphic features and early death

We report two sisters with a new syndrome of simplified gyral pattern, normal head circumference at birth but with subsequent development of microcephaly, intractable seizures, and early death. Dysmorphic features included coarse face, hypertrichosis, short nose, paranasal widening, long philtrum, short neck, upper limb micromelia, single transverse palmar lines, and clasp thumbs. The proband had repeated convulsions from shortly after birth and she required continuous artificial ventilation. Neurological examination showed absent sucking, rooting, Moro and grasping reflexes. MRI revealed a diffuse simplified gyral pattern with apparent agyria over the frontal lobes. Biochemical screening gave normal results. Her older sister had bilateral renal pelvic dilatation on prenatal ultrasound. She also developed severe convulsions on the first day of life, and she had to be artificially ventilated for 38 days. She had severe developmental retardation and neurological examination showed absence of spontaneous movements and Moro reflex, weak sucking reflex, and hypertonicity. CT scan of the brain showed a simplified gyral pattern. At 3 months, she developed hypocalcemia and hyperphosphatemia with normal levels of vitamin D and alkaline phosphatase, and parathyroid hormone level was low. Other biochemical tests gave normal results. She died at 5 months due to a massive aspiration event. Based on the unique clinical and radiological features found in our patients, we propose that this is a new syndrome.     

Mesenteric paraganglioma: a case report and review of the literature

Approximately 5% to 10% of paragangliomas occur in extra-adrenal sites, which can extend from the upper cervical region to the pelvis, parallel to the autonomic nervous system. This distribution corresponds to the embryologic development of the paraganglia from neural crest cells. Rarely, extra-adrenal paragangliomas can also occur aberrantly outside this distribution. We report such a case of extra-adrenal paraganglioma occurring in the anterior mesentery in a 76-year-old man. Two case reports exist in the literature describing extra-adrenal paragangliomas in the posterior mesentery. Normal paraganglionic tissue has been described at the roots of the superior and inferior mesenteric arteries, theoretically explaining the origin of the posterior mesenteric paragangliomas. Our case can best be attributed to the ventral migration of paraganglionic tissue through these vessels to reach the anterior mesentery, where they could potentially give rise to paragangliomas in this site.     

Effect of withaferin A on ehrlich ascites tumor cells. II. Target tumor cell destruction in vivo by immune activation

Intraperitoneal administration of Withaferin A 24 h after inoculation of Ehrlich ascites carcinoma resulted in an immediate inhibition of tumor growth, followed by complete disappearance of the malignant cells after 3-4 days. During this period a striking proliferation of macrophages in the peritoneal cavity and clustering of viable acid-phosphatase-rich macrophages around Ehrlich ascites tumor cells was observed. In addition, giant cell formation in the peritoneal cavity of the tumor-rejecting mice was commonly seen. No significant difference was found in the number of lymphocytes and polymorphonuclears of the peritoneal exudate of the tumor-rejecting mice as compared to untreated tumor-bearing mice. A similar sequence of changes with an even more striking proliferation of macrophages terminating again in complete tumor regression was observed after reinoculation of Ehrlich ascites cells to Withaferin A cured mice. Growth of Ehrlich ascites tumor cells in normal mice was prevented by passive transfer of serum or peritoneal cells, but not by spleen cells taken from immune mice. Humoral antibodies in the serum of immune mice were demonstrated by the complement fixation, the passive cutaneous anaphylaxis, and the cytotoxic tests. One-day-old suckling litters born to immune mothers were also refractory to Ehrlich ascites implantation. However, Ehrlich ascites cell growth was not affected if the litters were injected previously with a cell-free tumor homogenate.     

Lymphocyte activation: IV. The ultrastructural pattern of the response of mouse T and B cells to mitogenic stimulation in vitro

Thymocytes from cortisone-treated mice (`T' cells), `B' spleen cells (B lymphocytes from thymectomized, irradiated, marrow reconstituted mice) and normal spleen (T + B) cells were examined by electron microscopy after 60 hours stimulation by Concanavalin A (a T cell specific mitogen), endotoxin (B cell specific mitogen), and pokeweed mitogen (which stimulates both T and B cells). Stimulation of T cells by Con A or PWM induced the appearance of lymphoblasts (Type I) and only PWM or endotoxin stimulated B cells developed `plasmablast' features (dilated, vesicular rough endoplasmic reticulum; Type II). A few stimulated B cells also had lymphoblast morphology. Large cells from normal (T + B) spleen stimulated by PWM were heterogeneous consisting of 55–60 per cent plasmablasts and 40–45 per cent lymphoblasts. It was concluded that the ultrastructure of stimulated lymphocytes depended on whether T or B cells were stimulated and not primarily on the mitogen used. In general, the response evoked by mitogens paralleled at the ultrastructural level that induced by antigens. It was also found that multivesicular bodies and glycogen particles occurred predominantly in the cytoplasm of stimulated T cells (lymphoblasts).