Pharmacological evaluation of the cholinergic system in progressive supranuclear palsy

Severe cholinergic loss occurs in the brains of patients with progressive supranuclear palsy. To evaluate the functional implications of this neuronal deficit, dose-response curves were obtained in patients with progressive supranuclear palsy and normal control subjects undergoing intravenous cholinergic blockade (scopolamine) and stimulation (physo-stigmine). Physostigmine had no significant neurobehavioral effects at any does in patients with progressive supranuclear palsy. Scopolamine, at low and medium doses, significantly impaired memory performance of both groups, but worsened the gait of only the patients. High-dose scopolamine, which could not be tolerated by the patients, resulted in gait deterioration among control subjects. Thus, patients with progressive supranuclear palsy have increased sensitivity to cholinergic blockade compared to control subjects. Since loss of cholinergic neurons appears to contribute to the pathogenesis of certain cognitive and motor deficits found in progressive supranuclear palsy, the use of oral anticholinergics should ordinarily be avoided in this disorder. On the other hand, physostigmine at clinically tolerated dose levels seems to be terapeutically ineffective.     

Voltage-gated Currents in Rabbit Retinal Astrocytes

The voltage-gated currents of the astrocytes associated with the retinal capillaries of the rabbit retina were studied using whole-cell patch clamp recording. The resting potential of these cells was −70 ± 4.8 mV (mean ± SEM; n = 54), and the input resistance and cell capacitance were 558 ± 3.6 MΩ and 19.5 ± 1.8 pF respectively. Depolarization to potentials positive to −50 mV evoked rapidly activating inward and outward currents. The inward current was transient, eliminated by substitution of choline for Na⁺ in the bathing solution, and reduced by 50% in the presence of 1 μM tetrodotoxin. The time-to-peak of the Na⁺ current was more than twice that for the Na⁺ current found in retinal neurons. The glial Na⁺ current was half-inactivated at −55 mV. A transient component of the outward K⁺ current was blocked by external 4-aminopyridine while a more sustained component was blocked by external tetraethylammonium. At potentials between −150 and −50 mV the membrane behaved Ohmically. Voltage-gated currents in retinal astrocytes recorded in situ appear qualitatively similar to those described for some glial cells in vitro.     

Preoperative oral naproxen for pain relief after day-case laparoscopic sterilization

Analgesia with preoperative naproxen after laparoscopic sterilization was assessed in a prospective, double-blind, randomized study of 80 women; 42 women received oral naproxen 1 g, approximately 90 min before surgery, and 38 received placebo. Preoperative naproxen did not significantly influence postoperative pain scores, but was associated with a reduction in parenteral opioid administration (P = 0.04).      

Dynamic response of the occipito-atlanto-axial (C0-C1-C2) complex in right axial rotation.

The torque-angular deformation in right axial rotation until failure of the ligamentous occipito-atlanto-axial complex subjected to variable loading rate (dynamic) axial torque was characterized using a biaxial MTS system. A special fixture and gear box that permitted right axial rotation of the specimen until failure without imposing any additional constraints were used to obtain the data. The specimens were divided into three groups and tested until failure at three different dynamic loading rates: 50, 100, and 400 degrees/s. A previous study by the authors provided data for quasi-static (4 degrees/s) loading conditions. The torque versus rotation curves can be divided into two straight regions and two transition zones. The plots clearly indicated that at loading rates higher than 4 degrees/s, the specimens became stiffer in the region of steadily increasing resistance prior to failure. The increase in stiffness was maximum at 100 degrees/s. The stiffness decreased somewhat at 400 degrees/s in comparison with 100 degrees/s, but this decrease was not significant. The resulting torque-right axial rotation curves were also examined to estimate the magnitude of maximum resistance (torque) and the corresponding angular rotation value. The average maximum resistance torque increased from 13.6 Nm at 4 degrees/s to 27.8 Nm at 100 degrees/s. The corresponding right angular rotation data (65-78 degrees), however, did not show any significant variation with loading rate. Posttest dissection of the specimens indicated that the type of injury observed was related to the rate of axial loading imposed on a specimen during testing.(ABSTRACT TRUNCATED AT 250 WORDS)     

No Worries, No Cares: An Investigation into Self-Reported "Nondistress" in College Students

An important methodological issue in depressionanalog research is whether individuals who scoreextremely low on self-report measures like the BeckDepression Inventory (BDI) should be included innondepressed control groups. Joiner, Schmidt, and Metalsky(1994) found that college students with BDI scores of 0or 1 evidenced a fake-good test taking style as measuredby the MMPI validity scales. The present study investigated whether very low BDI scores (BDI= 0 or 1; n = 21) might be associated with an elevatedpositive mood state, extreme optimism, positiveattributional style or social desirability. Resultsindicated that the very low scoring BDI subjects scoredhigher on social desirability than the low scoring group(BDI = 2 9, n = 63). Significant differences on mood,symptom and cognitive measures disappeared when social desirability was entered as a covariate.Findings support Kendall, Hollon, Beck, Hammen, andIngram's (1987) recommendation that subjects who score0 or 1 on the BDI should be excluded from a nondepressed control group.     

Toxicology screening of the trauma patient: a changing profile

STUDY OBJECTIVES: To determine the current ingestants found in the multiply injured trauma patient and to determine if this select group of ingestants affected the resuscitation, evaluation, or convalescent management of these patients. DESIGN: A one-year retrospective analysis was performed on all patients who were admitted to an urban trauma center with a discharge diagnosis of multiple trauma and who received a comprehensive toxicology screening test. MAIN RESULTS: One hundred twenty-seven of the 177 patients (72%) who fulfilled the criteria had positive toxicology screens. Ethyl alcohol was the only drug present in 26 of these patients (20%); 57 (45%) were positive for drugs other than ethyl alcohol. A combination of ethyl alcohol and at least one other drug was quantified in 44 patients (35%). The most often encountered substances were ethyl alcohol (55%), marijuana (24%), and cocaine (21%). Twelve drug screens (9%) demonstrated pharmaceuticals (eg, acetylsalicylic acid, acetaminophen, or cyclic antidepressants) that may require specific antidotal treatment. CONCLUSION: The ingestant profile found in this subgroup of trauma patients differed from those of previous studies. Although a select group of these ingestants requires specific treatment or affects the physical assessment of the patient, none of these trauma patients received more than supportive care.     

Anti-leukemia effect of perillyl alcohol in Bcr/Abl-transformed cells indirectly inhibits signaling through Mek in a Ras- and Raf-independent fashion.

PURPOSE: Perillyl alcohol (POH) displays preventive and therapeutic activity against a wide variety of tumor models, and it has been suggested that this might be associated with the ability of POH to interfere with Ras prenylation. POH also selectively induces G(1) arrest and apoptosis in Bcr/Abl-transformed hematopoietic cells. Because signaling through Ras is necessary for Bcr/Abl transformation, we examined whether POH induces its anti-leukemia effect by inhibiting Ras signaling. EXPERIMENTAL DESIGN: The ability of POH to inhibit posttranslational farnesylation and signaling from Ras as well as signaling through the Raf-Mek-Erk cascade was examined in Bcr/Abl-transformed and mock-transformed cells and related to the anti-leukemia effect of POH. RESULTS: POH does not affect Ras prenylation or Ras activity, but it blocks signaling downstream of Ras by reversing the state of activation of the Erk kinase, Mek. POH affects Mek activity only when it is added to intact cells. Treatment of either cell lysates or of purified Mek with POH has no effect on Mek activity. Inhibition of the Mek-Erk pathway seems to be related to the POH anti-leukemia effect for the following reasons: (a) the concentration of POH needed to block the Erk pathway, as well the kinetics with which POH inhibits this signaling cascade, both correlate with the anti-leukemia effect of POH; (b) both U0126 (a specific Mek inhibitor) and POH induce similar anti-leukemia effects; and (c) mock-transformed hematopoietic cells are simultaneously resistant to POH anti-leukemia effects and inhibition of the Mek-Erk pathway. CONCLUSION: Blocking Mek is sufficient to induce growth arrest and apoptosis in Bcr/Abl-transformed cells; therefore, POH represents a novel small molecule inhibitor of Mek that might be effective for treating Bcr/Abl leukemias.     

Predictive power of various models for longitudinal attachment level change

Abstract Several statistical models that have been suggested in the periodontal literature for describing longitudinal attachment level changes, such as the gradual loss, single-burst, multiple-burst, and random walk models as well as other models introduced in this paper are compared by their power to predict future attachment loss. The data used in this analysis is from 1061 sites of 8 subjects, with moderate to severe periodontal disease, monitored monthly for about a year. This study found that none of the suggested models could significantly outperform the naive mean predictor, which predicts the future attachment level from the past mean. It was also found that no single model, such as the burst, gradual, or random walk, together with measurement error can fully explain the variation in the data. These results indicate that in the course of one year, the attachment level change may not follow the same model. Consequently, a model that fits well to past data cannot be accurately extended to the future.