Spatial gradients of cytosolic calcium concentration in neurones during paradoxical activation by calcium

PURPOSE: To assess long-term survival following cladribine salvage treatment for previously treated patients with chronic lymphocytic leukemia. PATIENTS AND METHODS: Fifty-two patients aged 39-84 years with previously treated CLL received cladribine 0.12 mg/kg/day in 2-hour infusions for 5 days in monthly courses. Two-thirds were refractory to previous therapy, and 8 had prior fludarabine. RESULTS: Sixteen (31%) patients achieved complete response (CR) and 14 (27%) partial remission (PR) according to consensus criteria. Response correlated with clinical stage, number of previous treatment regimes, blood lymphocyte count, and lymphocyte halflife following the first cladribine course. Toxicity included pneumonia (n = 9), herpes zoster (n = 7), and septicemia (n = 2). Four patients in CR underwent high-dose chemotherapy with autologous blood stem cell support, and 2 remain in CR 48 and 60 months from start of cladribine, and 2 had relapse at 42 and 48 months, respectively. Median progression-free survival (Kaplan-Meier analysis) for CR patients was 23 months from start of cladribine treatment, and for PR patients 16 months. The projected overall survival was 80% at 3 years for CR patients, and the median survival 28 months for PR patients and 4 months for non-responding patients. CONCLUSIONS: Our previous finding of durable CRs from cladribine in advanced CLL is thus confirmed in a larger patient material, and follow-up indicate that long-term survival may be achieved.     

Outbreak of serogroup C meningococcal disease associated with campus bar patronage

Between February 1991 and April 1992, eight undergraduates at a US residential university and one at a nearby 2-year college contracted serogroup C meningococcal disease. A case-control investigation with 20 controls per case, oropharyngeal carriage surveys, and multilocus enzyme electrophoresis (MEE) of serogroup C isolates were used to identify factors contributing to the outbreak. All eight sterile-site isolates from cases were closely related by MEE and were similar (though not identical) to the strain associated with the 1991-1992 epidemic of meningococcal disease in eastern Canada. Disease was associated with cigarette smoking (p = 0.012), recent patronage of campus-area bars (p = 0.034), estimated amount of time spent in campus-area bars (p = 0.0003), and, especially, recent patronage of one specific bar, bar A (p = 0.0006; odds ratio = 23.1, 95% confidence interval 3.0-571.5). In carriage surveys, 1,528 throat cultures taken from (primarily student) noncases yielded only five (0.3%) strains that were identical by MEE to those from cases. Two of these were found among 22 cultures obtained from bar A employees in spring 1992. Some cases in this outbreak may have followed transmission of the epidemic strain in bar A. Campus bar environments may facilitate the spread of meningococcal disease among teenagers and young adults.     

Conventional drug therapy in inflammatory bowel disease

The conventional treatment of inflammatory bowel disease should center around the liberal use of one of the many available forms of 5-ASA. Sulfasalazine should be used initially with the newer mesalamine-only containing drugs being reserved for sulfasalazine-intolerant patients or for those patients who require larger doses of medication. The choice of the delivery method should be made with the knowledge of the extent of disease and the potential coverage areas of the individual delivery methods. Systemic and topical glucocorticoids are an invaluable adjunct to 5-ASA therapy, but their use must be directed with the goal of remission induction. The tapering of glucocorticoids should be as prompt as the maintenance of remission allows, with a useful general guideline of decreasing the dose by 1 mg per day. Immunosuppressive therapy, including azathioprine and 6-mercaptopurine, holds promise for refractory cases of inflammatory bowel disease and for their potential steroid sparing properties; antibiotic therapy with metronidazole and ciprofloxacin in the absence of documented infectious disease offers additional routes to control disease. The majority of patients require a combination of drugs to attain remission. Only further study will reveal the ideal regimen for each of the different subsets of inflammatory bowel disease.     

Inhaled induction and emergence from desflurane anesthesia in the ambulatory surgical patient: the effect of premedication

We studied the effect of premedication (1 microgram/kg fentanyl and 0.04 mg/kg midazolam 5 min before induction of anesthesia) on airway reactivity and hemodynamic stability during inhaled induction using desflurane in 10 ambulatory surgical patients. Eight patients who were anesthetized without premedication served as the controls. Induction and emergence were rapid and unaffected by premedication. End-tidal and inspired concentrations of desflurane at loss of consciousness were significantly reduced by premedication (10.1% end-tidal/14.1% inspired, no premedication, vs. 5.3% end-tidal/8.9% inspired, premedication). Airway irritability was markedly attenuated by premedication (100% no premedication versus 30% premedicated), as was apnea (37.5% no premedication versus 0% premedicated). We observed an increase in mean arterial blood pressure and heart rate after loss of consciousness (mean arterial pressure 103 vs 121 mm Hg, heart rate 73 vs 100 bpm) in the unpremedicated patients, whereas both groups demonstrated a decrease in mean arterial blood pressure with no change in heart rate when baseline values were compared to those at incision (103 vs 74 mm Hg, no premedication, 99 vs 81 mm Hg premedicated). Patient acceptability was satisfactory and unchanged by premedication. We recommend the use of such premedication when desflurane is used during the induction of anesthesia.     

On Toroidal Azulenoids and Other Shapes of Fullerene Cage

The possibility of toroidal cages of carbon with repeating five and seven membered ring pairs (azulene units) upon their surfaces is briefly discussed. Some of the difficulties in recognising possible fullerene cage shapes are pointed out.     

Topology and Stability of Trivalent Polyhedral Clusters

An algorithm to generate the molecular graphs of the trivalent clusters is presented. All the polyhedral trivalent cages with 4-16 vertices are enumerated, with particular attention being given to their symmetry, spectra and stability. The relative stability of isomers is not decided solely by their symmetry. A new kind of spectral phenomenon is reported. This is the occurrence of graphs having the same HOMO-LUMO gap, the same E and the same even-order moments. We refer to it as 'pseudo-isospectrality'.     

Appraisal as a Pervasive Determinant of Anger.

L. Berkowitz and E. Harmon-Jones (see record 2004-15096-001) challenge appraisal theories of emotion by describing 2 sets of conditions (physical discomfort and anger-related muscle actions) in which anger appears to be elicited in the absence of theoretically predicted appraisals. In response, the authors discuss the ability of the specific appraisal model they have developed (e.g., C. A. Smith & L. D. Kirby, 2000, 2001; C. A. Smith & R. S. Lazarus, 1990) to account for such instances of anger. First, a number of issues are clarified relevant to the authors' model, including the nature of both the cognitive operations underlying appraisal and the specific appraisals hypothesized to evoke anger. The authors then describe how their model can account for the instances of anger described by L. Berkowitz and E. Harmon-Jones and how both accounts might be tested. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Early axon outgrowth of retinal ganglion cells in the fetal rhesus macaque

Employing retinal explants and retrograde transport techniques, we studied the formation of the arcuate fascicles by examining the growth of the central retina, the emergence of the adult fiber layer pattern, and the projections of retinal ganglion cells in the central and peripheral retina. Sixty days prior to foveal pit formation, the distance from the incipient fovea to the optic disk was equal to the adult, even though the retinal area was only 8% of the adult. Arcuate fibers, at this age, were observed to avoid the incipient fovea, with no fascicles and few axons projecting over this region. A small population of 15.2% of the ganglion cells located within 2 mm of the incipient fovea possessed an axon with an aberrant trajectory that wound around and projected 50 to several hundred microns away from the optic disk, compared to only 3% at other retinal locations. The incidence of disorder decreased with increasing fetal age, establishing mature values in late fetal periods. These findings suggest that the area of the central retina does not increase after embryonic day 60 and that guidance factors are present that allow outgrowing ganglion cell axons to distinguish and avoid that portion of the retina that will become the fovea.     

Use of subunit-specific antisense oligodeoxynucleotides to define developmental changes in the properties of N-methyl-D-aspartate receptors

Antisense oligodeoxynucleotides were used to determine whether alterations in the expression of N-methyl-D-aspartate (NMDA) receptor subunit mRNA are responsible for developmental changes in the sensitivity of receptors to agonists and antagonists. Xenopus laevis oocytes were injected with mRNA prepared from neonatal and adult rat cerebral cortex, and the effects of agonists and antagonists were determined under voltage-clamp conditions. Glycine-site antagonists like 7-chlorokynurenate and glutamate-site antagonists like CGP-39653 were more potent at NMDA receptors expressed from mRNA from adult rat cerebral cortex than those expressed from mRNA from 1-day-old rat. NMDA receptors from 1-day-old rat cerebral cortex were more sensitive to activation by glycine than were receptors from adult rat cerebral cortex. 7-Chlorokynurenate and CGP-39653 were more potent inhibitors of responses seen with heteromeric NR1/NR2A receptors than with NR1/ NR2B receptors. Conversely, heteromeric NR1/NR2B receptors were more sensitive to activation by glycine than were NR1/NR2A receptors. We previously described a delay in the expression of the NR2A subunit in developing rat brain. Anti-sense oligodeoxynucleotides were used to determine whether the delayed expression of the NR2A subunit underlies changes in pharmacological properties observed during development. The properties of receptors seen when adult brain mRNA was coinjected with antisense oligodeoxynucleotides against the NR2A subunit were similar to those found in receptors from 1-day-old rat brain. These data suggest that changes in the sensitivity of NMDA receptors to antagonists and to glycine seen during development are a result of alterations in the expression of different species of NR2 subunit mRNA.