Second case report of del(4) (q25q27) and review of the literature

We report a malformed infant with a de novo interstitial deletion of 4q. This is the second patient reported with del(4) (q25q27). Although there are several common features such as marked hypotonia, cardiac abnormalities, cleft palate, and micrognathia noted in our case and that of Chudley et al. (1988), we conclude from our comparison of the seven previously reported cases involving deletions of bands 4(q25q27) that a specific phenotype cannot yet be described for this deletion.     

Influence of Hemorrhagic Shock Followed by Crystalloid Resuscitation on Propofol: A Pharmacokinetic and Pharmacodynamic Analysis

Background: Previous work has demonstrated that ongoing hemorrhagic shock dramatically alters the distribution, clearance, and potency of propofol. Whether volume resuscitation after hemorrhagic shock restores drug behavior to baseline pharmacokinetics and pharmacodynamics remains unclear. This is particularly relevant because patients suffering from hemorrhagic shock are typically resuscitated before surgery. To investigate this, the authors studied the influence of an isobaric bleed followed by crystalloid resuscitation on the pharmacokinetics and pharmacodynamics of propofol in a swine model. The hypothesis was that hemorrhagic shock followed by resuscitation would not significantly alter the pharmacokinetics but would influence the pharmacodynamics of propofol.

Methods: After approval from the Animal Care Committee, 16 swine were randomly assigned to control and shock-resuscitation groups. Swine randomized to the shock-resuscitation group were bled to a mean arterial blood pressure of 40 mm Hg over a 20-min period and held there by further blood removal until 42 ml/kg of blood had been removed. Subsequently, animals were resuscitated with lactated Ringer's solution to maintain a mean arterial blood pressure of 70 mm Hg for 60 min. After resuscitation, propofol (750 [mu]g[middle dot]kg-1[middle dot]min-1) was infused for 10 min. The control group underwent a sham hemorrhage and resuscitation and received propofol at the same dose and approximate time as the shock-resuscitation group. Arterial samples (20 from each animal) were collected at frequent intervals until 180 min after the infusion began and were analyzed to determine drug concentrations. Pharmacokinetic parameters for each group were estimated using a three-compartment model. The electroencephalogram Bispectral Index Scale was used as a measure of drug effect. Pharmacodynamics were characterized using a sigmoid inhibitory maximal effect model.

Results: The raw data demonstrated minimal differences in the mean plasma propofol concentrations between groups. The compartment analysis revealed some subtle differences between groups in the central and slow equilibrating volumes, but the differences were not significant. Hemorrhagic shock followed by resuscitation shifted the concentration effect relationship to the left, demonstrating a 1.5-fold decrease in the effect-site concentration required to achieve 50% of the maximal effect in the Bispectral Index Scale.     

GM1 ganglioside partially rescues cultured dopaminergic neurons from MPP-induced damage: dependence on initial damage and time of treatment

GM1 ganglioside is believed to be important in promoting the recovery of neurons from injury. The present study assesses the ability of GM1 to repair or prevent the damage of dopamine neurons caused by the neurotoxin 1-methyl-4-phenylpyridinium (MPP⁺). Treatment of mesencephalic cell cultures with 2.5 μM MPP⁺ resulted in the loss of 30% of tyrosine hydoxylase (TH) immunoreactive neurons. In contrast, cultures administered 100 μM GM1 ganglioside for 3 days after toxin treatment contained nearly control numbers of TH⁺ neurons (97%). This reparative effect of GM1 was reflected in parallel increases in TH enzyme activity, dopamine and dopac levels. Cultures sustaining greater insult from higher doses of MPP⁺ (5.0–10.0 μM) did not benefit from ganglioside treatment, suggesting that rescue by GM1 depended on the degree of initial damage to cells. Moreover, the timing of ganglioside treatment was critical; pretreatment with GM1 alone did not prevent or attenuate the damage caused by subsequent incubation in 2.5 μM MPP⁺.     

Outpatient Laparoscopic Cholecystectomy

Outpatient Laparoscopic Cholecystectomy was attempted in 98 patients selected from 266 patients presenting for elective cholecystectomy (37%). Two patients required admission following conversion to “open” Cholecystectomy, one patient was admitted for observation because of a technically difficult Laparoscopic Cholecystectomy and 16 patients were admitted because of refractory nausea and vomiting in the early post-operative period. Seventy-nine patients (81%) were able to be discharged home within 4 to 6 hours of surgery, with only one patient requiring readmission to hospital because of the onset of nausea and vomiting. There were no post-operative complications attributable to the outpatient experience. We believe this approach to elective gallbladder pathology can be safely accomplished in selected patients and will be increasingly utilized in the future.     

Comparison of ultrasonic cleaning schemes: a pilot study.

OBJECTIVE: Ultrasonic cleaning is an effective method for cleaning dental instruments prior to sterilisation. However, there are few studies that directly compare precleaning and ultrasonic cleaning solutions. This study evaluated the efficacy of different ultrasonic cleaning schemes. METHOD AND MATERIALS: Twenty representative dental instruments, five of which were soiled with a mixture of blood and hydroxyapatite, were used in a series of cleaning runs. Cleaning employed a presoaking agent, ultrasonic cleaning, or a combination of both. Two presoaking agents (Non-ionic Ultrasonic Cleaning Solution and ProEZ Foaming Enzymatic Spray) plus five ultrasonic cleaners (UltraDose, General Purpose Cleaner, Co-enzyme Concentrate, Enzol Enzymatic Detergent, and Non-ionic Ultrasonic Cleaning Solution) were compared, with tap water serving as a control. There were two cleaning times: seven and 15 minutes. After rinsing, the working ends of the instruments underwent scrubbing for 20 seconds using a dental polishing brush held in a haemostat. After scrubbing, the brush and instrument were placed in a tube containing sterile saline. Vortexing of the tube lasted 30 seconds. Testing for the post-cleaning presence of blood involved Hemastix dipsticks. These sticks measure minute amounts of blood in urine and can detect as few as 35 red blood cells per ml. Comparisons of colour change were made to a standard scale followed by assignment of numeric values. RESULTS: Tap water was the poorest cleaning solution, while UltraDose was the most effective. Blood removal improved when cleaning time was increased from seven to 15 minutes. The combined effect of a presoak immersion followed by ultrasonic cleaning was the most effective cleaning scheme overall. Cleaning by either ultrasound or presoaking only was less effective. Some instruments were more difficult to clean than others. CONCLUSION: Within the constraints of the small number of test runs performed, it was concluded that application of a presoak agent before ultrasonic cleaning produced the most effective instrument-cleaning regimen.     

The striatal-enriched protein tyrosine phosphatase gates long-term potentiation and fear memory in the lateral amygdala.

BACKGROUND: Formation of long-term memories is critically dependent on extracellular-regulated kinase (ERK) signaling. Activation of the ERK pathway by the sequential recruitment of mitogen-activated protein kinases is well understood. In contrast, the proteins that inactivate this pathway are not as well characterized. METHODS: Here we tested the hypothesis that the brain-specific striatal-enriched protein tyrosine phosphatase (STEP) plays a key role in neuroplasticity and fear memory formation by its ability to regulate ERK1/2 activation. RESULTS: STEP co-localizes with the ERKs within neurons of the lateral amygdala. A substrate-trapping STEP protein binds to the ERKs and prevents their nuclear translocation after glutamate stimulation in primary cell cultures. Administration of TAT-STEP into the lateral amygdala (LA) disrupts long-term potentiation (LTP) and selectively disrupts fear memory consolidation. Fear conditioning induces a biphasic activation of ERK1/2 in the LA with an initial activation within 5 minutes of training, a return to baseline levels by 15 minutes, and an increase again at 1 hour. In addition, fear conditioning results in the de novo translation of STEP. Inhibitors of ERK1/2 activation or of protein translation block the synthesis of STEP within the LA after fear conditioning. CONCLUSIONS: Together, these data imply a role for STEP in experience-dependent plasticity and suggest that STEP modulates the activation of ERK1/2 during amygdala-dependent memory formation. The regulation of emotional memory by modulating STEP activity may represent a target for the treatment of psychiatric disorders such as posttraumatic stress disorder (PTSD), panic, and anxiety disorders.     

When Is a Bispectral Index of 60 Too Low?: Rational Processed Electroencephalographic Targets Are Dependent on the Sedative-Opioid Ratio

Background: Opioids are commonly used in conjunction with sedative drugs to provide anesthesia. Previous studies have shown that opioids reduce the clinical requirements of sedatives needed to provide adequate anesthesia. Processed electroencephalographic parameters, such as the Bispectral Index (BIS; Aspect Medical Systems, Newton, MA) and Auditory Evoked Potential Index (AAI; Alaris Medical Systems, San Diego, CA), can be used intraoperatively to assess the depth of sedation. The aim of this study was to characterize how the addition of opioids sufficient to change the clinical level of sedation influenced the BIS and AAI.

Methods: Twenty-four adult volunteers received a target-controlled infusion of remifentanil (0-15 ng/ml) and inhaled sevoflurane (0-6 vol%) at various target concentration pairs. After reaching pseudo-steady state drug levels, the modified Observer's Assessment of Alertness/Sedation score, BIS, and AAI were measured at each target concentration pair. Response surface pharmacodynamic interaction models were built using the pooled data for each pharmacodynamic endpoint.

Results: Response surface models adequately characterized all pharmacodynamic endpoints. Despite the fact that sevoflurane-remifentanil interactions were strongly synergistic for clinical sedation, BIS and AAI were minimally affected by the addition of remifentanil to sevoflurane anesthetics.