Response latencies to visual stimulation and disparity sensitivity in single cells of the awake Macaca mulatta visual cortex

The onset response latencies to dynamic random dot figures (solid figures) and dynamic random dot stereograms were measured in single units recorded from areas V1 and V2 of two awake Macaca mulatta monkeys. We studied 56 cells, 39 from V1 and 17 from V2. In 14 disparity sensitive and 13 disparity unsensitive cells from V1 the median latencies to solid figures were 59.8 and 73.6 ms, respectively, which were statistically different. In 26 disparity sensitive cells from V1 and 17 from V2 the median latencies to stereofigures were 85.6 and 97.9 ms, respectively, which were statistically different. These results indicate that V1 disparity sensitive cells may have shorter integration time than disparity unsensitive cells and that there is a transferring delay for disparity information between areas V1 and V2.     

Chronic obstructive pulmonary disease patients with invasive pulmonary aspergillosis: benefits of intensive care?

OBJECTIVES: Invasive pulmonary aspergillosis (IPA) is increasingly recognized as a cause of acute respiratory failure in patients with chronic obstructive pulmonary disease (COPD) treated with corticosteroids. For these patients admission in intensive care unit (ICU) is often required for life-support and mechanical ventilation. Whether this approach improves outcome is unknown. DESIGN AND SETTING: Retrospective study in a university hospital intensive care unit. PATIENTS: Between November 1993 and December 1997, 23 COPD patients were admitted in our ICU and received antifungal agents for possible IPA. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The clinical features and the outcome were reviewed. Diagnosis of IPA was classified as confirmed (positive lung tissue biopsy and/or autopsy) or probable (repeated isolation of Aspergillus from the airways with consistent clinical and radiological findings). Among the 23 patients treated for Aspergillus, 16 fulfilling these criteria for IPA were studied. Steroids had been administered at home to all patients but one and were increased during hospitalization in all. Twelve patients suffered a worsening of their bronchospasm precipitating acute respiratory failure. During ICU stay all patients required mechanical ventilation for acute respiratory failure. Although amphotericin B deoxycholate was started when IPA was suspected (0.5-1.5 mg/kg per day), all patients died in septic shock (n = 5) or in multiple-organ failure. CONCLUSIONS: The poor prognosis of intubated COPD patients with IPA, in spite of antifungal treatment suggests that further studies are required to define the limits and indications for ICU management of these patients.     

Abdomen release in prone position does not improve oxygenation in an experimental model of acute lung injury

OBJECTIVE: To analyze the effect of abdomen release in the prone position on oxygenation in an experimental model of acute lung injury. DESIGN: Experimental randomized controlled study. SETTING: Experimental laboratory of a tertiary university hospital. PARTICIPANTS: Mixed-breed adolescent pigs weighing between 25-31 kg. INTERVENTIONS: Thirty minutes after pulmonary edema was produced with oleic acid, the animals were turned prone and randomized into two groups: group I or control (n = 9), lying directly on the operating table; and group II (n = 11) with abdomen release, with positioning rolls under the upper part of the chest wall and the pelvis to allow free movement of the abdomen. MEASUREMENTS AND RESULTS: The gas exchange, respiratory mechanics, hemodynamics, intra-abdominal pressure (IAP) and the extravascular lung water (EVLW), determined by double indicator dilution method (DI), were recorded at baseline (time 0) and at 30, 60, 90, 120 and 150 min. The PaO2/FIO2 increased in both groups at 30 min after the pigs were placed in the prone position (time 60) and then decreased progressively until the end of the experimental period, with no statistical differences between the groups at any time (73.1 +/- 14.5 vs 79.5 +/- 14.9 at 150 min). Abdomen release was not associated with changes in the respiratory mechanics, EVLW or intra-abdominal pressure. CONCLUSIONS: Abdomen release in prone position does not improve oxygenation in an experimental model of acute lung injury.     

Transplant coordination program: a useful tool to improve organ donation in Venezuela

Donor shortage is the single most important limitation for allowing adequate growth of transplant programs. Transplant coordination programs have been shown to provide solutions to this situation worldwide. To evaluate the efficacy of transplant coordination programs in Venezuela, a pilot program was implemented at a 1200-bed teaching hospital. The implementation of this program included an assessment of the hospital's donation practices such as donor identification, maintenance, brain-death diagnosis, family consent for donation, and timely transport and allocation of organs and tissues. A follow-up 1 year after the implementation of the transplant coordination program demonstrated a 7-fold increase in the number of donors compared with the 2 previous years when the program did not exist. During the first year of application, the transplant coordination program resulted in solutions in how to address issues surrounding the procurement process in a hospital with a high potential donor rate; a linkage between the coordinator and the medical staff through educational activities; increased skills of hospital staff; and a methodology that should be applied extensively in hospitals with high donor potential to deal with the organ shortage.     

Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial

Context  The optimal duration of antimicrobial treatment for ventilator-associated pneumonia (VAP) is unknown. Shortening the length of treatment may help to contain the emergence of multiresistant bacteria in the intensive care unit (ICU). Objective  To determine whether 8 days is as effective as 15 days of antibiotic treatment of patients with microbiologically proven VAP. Design, Setting, and Participants  Prospective, randomized, double-blind (until day 8) clinical trial conducted in 51 French ICUs. A total of 401 patients diagnosed as having developed VAP by quantitative culture results of bronchoscopic specimens and who had received initial appropriate empirical antimicrobial therapy were enrolled between May 1999 and June 2002. Intervention  A total of 197 patients were randomly assigned to receive 8 days and 204 to receive 15 days of therapy with an antibiotic regimen selected by the treating physician. Main Outcome Measures  Primary outcome measures—death from any cause, microbiologically documented pulmonary infection recurrence, and antibiotic-free days—were assessed 28 days after VAP onset and analyzed on an intent-to-treat basis. Results  Compared with patients treated for 15 days, those treated for 8 days had neither excess mortality (18.8% vs 17.2%; difference, 1.6%; 90% confidence interval [CI], -3.7% to 6.9%) nor more recurrent infections (28.9% vs 26.0%; difference, 2.9%; 90% CI, -3.2% to 9.1%), but they had more mean (SD) antibiotic-free days (13.1 [7.4] vs 8.7 [5.2] days, P<.001). The number of mechanical ventilation–free days, the number of organ failure–free days, the length of ICU stay, and mortality rates on day 60 for the 2 groups did not differ. Although patients with VAP caused by nonfermenting gram-negative bacilli, including Pseudomonas aeruginosa, did not have more unfavorable outcomes when antimicrobial therapy lasted only 8 days, they did have a higher pulmonary infection-recurrence rate compared with those receiving 15 days of treatment (40.6% vs 25.4%; difference, 15.2%, 90% CI, 3.9%-26.6%). Among patients who developed recurrent infections, multiresistant pathogens emerged less frequently in those who had received 8 days of antibiotics (42.1% vs 62.0% of pulmonary recurrences, P = .04). Conclusions  Among patients who had received appropriate initial empirical therapy, with the possible exception of those developing nonfermenting gram-negative bacillus infections, comparable clinical effectiveness against VAP was obtained with the 8- and 15-day treatment regimens. The 8-day group had less antibiotic use.      

Parent-defined target symptoms respond to risperidone in RUPP autism study: customer approach to clinical trials

OBJECTIVE: A consumer-oriented efficacy assessment in clinical trials should measure changes in chief complaint and consumer request (symptoms of most concern to patient/caregiver), which may be diluted in change scores of multisymptom scales. METHOD: In the Research Units on Pediatric Psychopharmacology (RUPP) Autism Network 8-week double-blind trial of risperidone versus placebo, the chief concerns of parents were collected at 0, 4, and 8 weeks (endpoint), in addition to standardized primary measures. Blinded clinical judges rated change from baseline to 4 and 8 weeks on a 9-point scale (1 = normalized, 5 = unchanged, 9 = disastrous); 94 participants had usable data. RESULTS: The most common symptoms identified by parents were tantrums, aggression, and hyperactivity. Interrater reliability was excellent. Mean ratings at endpoint were 2.8 +/- 1.2 on risperidone and 4.5 +/- 1.3 on placebo (p <.001). Ratings were collinear with Clinical Global Impression-Improvement and Aberrant Behavior Checklist Irritability subscale (primary dimensional measure). Effect size d was 1.4, compared to 1.2 on the Aberrant Behavior Checklist Irritability subscale. Effect sizes varied twofold by symptom category, largest for self-injury (2.11) and tantrums (1.95). CONCLUSIONS: Risperidone was superior to placebo in reducing symptoms of most concern to parents of autistic children with irritable behavior. Rating individualized participant-chosen target symptoms seems a reliable, sensitive, efficient, and consumer-friendly way to assess treatment effect and might have clinical application.     

Audioverbal cognitive dysfunction in depression. Factors involved

There is increasing evidence suggesting that depression is associated with a certain degree of cognitive dysfunction. However, there is still debate on whether this dysfunction is only substantially associated with the most severe forms of depression, on whether or not it decreases in parallel with clinical response, and on the role played in these changes by psychotropic medications. In order to clarify these questions, we analyzed the performance in several cognitive tasks that involved attention and working memory of 40 untreated subjects with a diagnosis of dysthymia or major depressive disorder without melancholia. The protocol used included three audioverbal tasks: vocal reaction time (VRT), inverse spelling (IS) and text repetition (TR). The protocol was also administered to 20 healthy volunteers that were used as a comparison group. The same battery of assessments was administered 2 months later to all 60 subjects. At the time of the second assessment, patients (but not healthy volunteers) were on antidepressant medication, in accordance with common clinical practice. The authors found a longer VRT in patients versus healthy volunteers at baseline. VRT did not decrease in patients that responded to treatment. However, there was an improvement in VRT in patients that took sertraline (n=16) compared to subjects taking imipramine (n=11). This fact was not attributable to differences in antidepressant response. Performance in the two other tasks was globally worse in the patient group than in the comparison group, and there was also an absence of improvement in the scores of patients who responded to treatment. However, when the sample was stratified by illness duration, individuals with less than 10 years from the first episode of depression showed a decrease in IS errors compared to the healthy volunteers. It is concluded that patients with nonmelancholic depression suffer from cognitive dysfunction, that this dysfunction persists after clinical improvement and that at least attention is influenced by the type of medication taken. Time from onset of the disorder also seems to influence changes in cognitive performance.     

Pituitary adenylate cyclase-activating polypeptide prevents C2-ceramide-induced apoptosis of cerebellar granule cells

The sphingolipid metabolites, ceramides, are critical mediators of the cellular stress response and play an important role in the control of programmed cell death. In particular, ceramides have been shown to induce apoptosis of cerebellar granule cells. We show that pituitary adenylate cyclase-activating polypeptide (PACAP) prevents C2-ceramide-induced apoptosis. The neuroprotective effect of PACAP was dose-dependent and blocked by its antagonist, PACAP6-38, whereas the PACAP-related peptide VIP was inactive. The effect of PACAP on cell survival was mimicked by dibutyryl-cAMP (dbcAMP) and forskolin and prevented by the MEK inhibitor U0126, indicating that both the adenylyl-cyclase and MAP-kinase pathways contribute to the neuroprotective action of the peptide. C2-ceramide and PACAP induced opposite effects on phosphorylated forms of ERK and JNK without affecting the total amounts of ERK and JNK, suggesting that a balance between these two MAP-kinases is critical for the cell survival/death decision. The effect of PACAP on ERK phosphorylation was blocked by U0126, but was not affected by H89 or chelerythrine indicating that PACAP activates ERK through a PKA- and PKC-independent mechanism. C2-ceramide induced a time-dependent activation of caspase-3, enhanced the amount of cleaved caspase-3 and stimulated the DNA fragmentation process, while PACAP strongly inhibited the C2-ceramide-induced activation of caspase-3, reduced the expression of cleaved caspase-3 and blocked DNA fragmentation. Taken together, the present results show that C2-ceramide induces apoptosis of cerebellar granule cells through a mechanism involving activation of caspase-3. Our data also demonstrate that PACAP is a potent inhibitor of C2-ceramide-induced apoptosis.