Inhibition of apoptosis by hyperbaric oxygen in a rat focal cerebral ischemic model.

The hypothesis was tested that hyperbaric oxygen therapy (HBO) reduced brain infarction by preventing apoptotic death in ischemic cortex in a rat model of focal cerebral ischemia. Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) and subsequently were exposed to HBO (2.5 atmospheres absolute) for 2 h, at 6 h after reperfusion. Rats were killed and brain samples were collected at 24, 48, 72 h, and 7 days after reperfusion. Neurologic deficits, infarction area, and apoptotic changes were evaluated by clinical scores, 2,3,7-triphenyltetrazolium chloride staining, caspase-3 expression, DNA fragmentation assay, and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling (TUNEL)-hematoxylin and eosin (H&E) costaining. In MCAO/R without HBO treatment animals, DNA fragmentation was observed in injured cortex at 24, 48, and 72 h but not in samples at 7 days after reperfusion. Double labeling of brain slides with NeuN and caspase-3 demonstrated neurons in the injured cortex labeled with caspase-3. TUNEL+H&E costaining revealed morphologic apoptotic changes at 24, 48, and 72 h after reperfusion. Hyperbaric oxygen therapy abolished DNA fragmentation and reduced the number of TUNEL-positive cells. Hyperbaric oxygen therapy reduced infarct area and improved neurologic scores at 7 days after reperfusion. One of the molecular mechanisms of HBO-induced brain protection is to prevent apoptosis, and this effect of HBO might preserve more brain tissues and promote neurologic functional recovery.     

Evidence for a distinct nigropallidal dopaminergic projection in the squirrel monkey

Injections of the retrograde fluorescent tracer fast blue in the striatum (STR) and nuclear yellow in the internal segment of the globus pallidus (GPi) in the squirrel monkey (Saimiri sciureus) revealed a nigropallidal projection whose cellular origin was largely distinct from that of the nigrostriatal pathway. Neurons containing the tracer injected in GPi were scattered throughout the substantia nigra-ventral tegmental area complex where they formed approximately 20-25% of the total number of retrogradely labeled cells. Only about 5-10% of all positive neurons were double-labeled after STR-GPi injections. In experiments combining the use of the fluorescent tracer propidium iodide with immunofluorescence, the majority of neurons projecting to GPi displayed tyrosine hydroxylase immunoreactivity. Hence, in addition to their important role at striatal level, midbrain dopaminergic neurons may influence directly the output neurons of the basal ganglia at pallidal level in primates.     

Diagnostic value of D-dimer in patients with suspected pulmonary embolism: results from a multicentre outcome study

BACKGROUND: D-dimer tests are used in various diagnostic strategies to exclude pulmonary embolism (PE). However, their role as an exclusionary first-line test is still uncertain, mainly because accuracy of the test varies according to the assay and the studied population. METHODS: The aim of this multicentre study was to evaluate the accuracy of D-dimer testing in patients with suspected PE. Diagnosis of PE was based on pre-test clinical probability (PCP) evaluation and both single-detector spiral CT (CT) and lower limbs compression ultrasonography (CUS). Lung scanning and/or pulmonary angiography was mandatory when CT or CUS was inconclusive and when both CT and CUS were normal in a patient with a high PCP. All patients were followed-up for 3 months, looking for VTE recurrence. D-dimers were collected within 24 h of inclusion and stored in each local hematology unit, to be analyzed at the end of all inclusions; physicians in charge of the patient were blinded to D-dimer results. RESULTS: Three hundred and fifty two patients were included in 4 centres. Prevalence of PE was 38.6%. PCP was low in 82 (23.3%), intermediate in 176 (50%) and high in 94 (26.7%) patients. Sensitivity of D-dimer was 96.3% (95% CI: 93-99) and negative predictive value reached 94.4% (95% CI: 90-99). Five patients with a confirmed PE had a D-dimer level below 500 ng/ml (two patients with a high PCP). Among 258 patients with low or intermediate PCP, 80 (31%) had a negative D-dimer test result; three of them had a false negative result and the number needed to test was 3.3. Among 94 patients with a high PCP, 9 had a negative D-dimer test result; two of them had a false negative result and the number needed to test was 13.5. CONCLUSION: These results confirm that rapid assays used in this study can safely exclude PE in first-line testing only in non-high CP patients.     

Immune-tolerant elastin-like polypeptides (iTEPs) and their application as CTL vaccine carriers

Background: Cytotoxic T lymphocyte (CTL) vaccine carriers are known to enhance the efficacy of vaccines, but a search for more effective carriers is warranted. Elastin-like polypeptides (ELPs) have been examined for many medical applications but not as CTL vaccine carriers.

Purpose: We aimed to create immune tolerant ELPs using a new polypeptide engineering practice and create CTL vaccine carriers using the ELPs.

Results: Four sets of novel ELPs, termed immune-tolerant elastin-like polypeptide (iTEP) were generated according to the principles dictating humoral immunogenicity of polypeptides and phase transition property of ELPs. The iTEPs were non-immunogenic in mice. Their phase transition feature was confirmed through a turbidity assay. An iTEP nanoparticle (NP) was assembled from an amphiphilic iTEP copolymer plus a CTL peptide vaccine, SIINFEKL. The NP facilitated the presentation of the vaccine by dendritic cells (DCs) and enhanced vaccine-induced CTL responses.

Discussion: A new ELP design and development practice was established. The non-canonical motif and the immune tolerant nature of the iTEPs broaden our insights about ELPs. ELPs, for the first time, were successfully used as carriers for CTL vaccines.

Conclusion: It is feasible to concurrently engineer both immune-tolerant and functional peptide materials. ELPs are a promising type of CTL vaccine carriers.     

Moclobemide versus fluoxetine for a major depressive episode

The efficacy and tolerability of moclobemide (300–600 mg daily) and fluoxetine (20–40 mg daily) were compared in a 6-week, double-blind study of 65 inpatients and 34 outpatients suffering from major depressive episodes (DSM III-R). No statistically significant differences between the two treatment groups were noted regarding efficacy (HDRS, CGI) or safety (adverse events, laboratory examination, vital signs). Moclobemide (300–600 mg daily) and fluoxetine (20–40 mg daily) would thus appear to be comparable both in antidepressant efficacy and tolerability. Doubling the low dosage in non-responders after 3 weeks resulted in a statistically significant improvement of CGI in the moclobemide group by comparison with the fluoxetine group at study end, suggesting that 600 mg moclobemide/day can still improve the patient's condition, while 40 mg fluoxetine/day does not. Sexual dysfunction was reported in two patients taking fluoxetine.     

Predicting treatment success at multiple timepoints in diverse patient populations of cocaine-dependent individuals

The quest for predictive utility of baseline demographic and drug use characteristics has been difficult. The present article draws data from two studies of cocaine-dependent individuals (N = 297) in treatment at clinics in Los Angeles, and examines the utility of socio-demographic characteristics of patients and in-treatment performance variables as predictors of success at treatment end, 6 and 12 month follow-up assessments. Socio-demographic variables examined are age, gender, ethnicity, and educational attainment; drug use variables include years of cocaine use, self-reported days of cocaine use, the Addiction Severity Index drug composite score, and two composite measures cited in the literature. The in-treatment variables examined include cocaine urine toxicology results, number of weeks retained, and measures of compliance. The self-reported number of days of cocaine use in the past 30 days provides the most predictive utility of all baseline variables evaluated, and is the most parsimonious of the significant variables associated with substance use at all subsequent timepoints. Matching cocaine-dependent patients with treatment types or intensities based on the self-reported number of cocaine use days at intake may increase patient success rates.     

Hypoxic-ischemic injury stimulates subventricular zone proliferation and neurogenesis in the neonatal rat

Neurogenesis persists throughout life in the rodent subventricular zone (SVZ) and increases in the adult after brain injury. In this study, postnatal day 7 (P7) rats underwent right carotid artery ligation followed by 8% O2 exposure for 90 min, a lesioning protocol that resulted in ipsilateral forebrain hypoxic-ischemic (HI) injury. The effects of HI injury on SVZ cell proliferation and neurogenesis were examined 1-3 wk later by morphometric measurement of dorsolateral SVZ size; by immunoassays to detect incorporation of bromodeoxyuridine (BrdU) in proliferating cells; and by immunoassays of doublecortin, a microtubule-associated protein expressed only by immature neurons. For determining the cell phenotypes of newly generated cells, tissue sections were double labeled with antibodies to BrdU and markers of mature neurons (neuronal nuclear protein), astrocytes (glial fibrillary acidic protein), or oligodendroglia (RIP). HI injury resulted in enlargement of the ipsilateral SVZ at P14-28 and a corresponding increase in BrdU cell numbers both in the ipsilateral SVZ and striatum at P21. HI injury also stimulated SVZ neurogenesis, based on increased doublecortin immunostaining in the SVZ ipsilateral to lesioning at P14-28. However, 4 wk after HI injury, in the lesioned striatum, although BrdU/glial fibrillary acidic protein and BrdU/RIP-labeled cells were identified, no BrdU/neuronal nuclear protein double-labeled cells were found. These results suggest that although acute neonatal HI injury stimulates SVZ proliferation and neurogenesis, there is inadequate trophic support for survival of newly generated neurons. Identification of the trophic factors that enhance maturation and survival of immature neurons could provide important clues for improving recovery after neonatal brain injury.     

Quality of life of patients with high-grade spondylolisthesis: minimum 2-year follow-up after surgical and nonsurgical treatments

Background contextSurgical intervention is generally indicated in a pediatric high-grade spondylolisthesis to prevent the progression of deformity or neurologic deterioration and improve the quality of life. However, the outcome of the treatment on the health-related quality of life (HRQOL) of patients with high-grade spondylolisthesis remains largely unknown.PurposeTo describe the changes in the HRQOL of patients with pediatric high-grade spondylolisthesis after surgical and nonsurgical managements.Study designObservational case series with a minimal of 2-year follow-up.Patient sampleTwenty-eight pediatric patients with high-grade spondylolisthesis from a single institution filled the inclusion criteria. Twenty-three patients were managed surgically and five were managed nonsurgically.Outcome measuresSelf-report measures: Scoliosis Research Society questionnaires (SRS-22). Neurologic examination, radiographic evaluation of slip grade.MethodsThe SRS-22 questionnaire was collected at the baseline (initial presentation for the nonsurgical group and preoperative visit for the surgical group) and at the last follow-up. Differences between baseline and last follow-up were evaluated in both groups. Correlation between the baseline score of SRS-22 score and improvement in the SRS-22 score was determined in surgical patients.ResultsIn surgical patients, total SRS-22 scores were 3.31±0.50 at the baseline and 4.26±0.50 at the last follow-up. In nonsurgical patients, total SRS-22 scores were 4.12±0.16 at the baseline and 4.14±0.38 at the last follow-up. Therefore, variation in the SRS-22 total score was +0.94±0.77 (p<.001) for surgical patients and +0.02 ± 0.35 (p=.854) for nonsurgical patients. Improvement of the SRS-22 score was correlated with a low baseline value of SRS-22 (R²=0.61; p<.001). There was no neurologic or slip deterioration during the follow-up for patients treated nonsurgically.ConclusionsThe HRQOL improves after a surgical intervention for high-grade spondylolisthesis. Patients with lower baseline HRQOL scores are those who benefit the most from surgery. Close observation is a safe and feasible option in selected patients with a good baseline HRQOL and no neurologic impairment.     

Evaluation of safety and tolerance of microencapsulated Lactobacillus reuteri NCIMB 30242 in a yogurt formulation: A randomized,placebo-controlled,double-blind study

Probiotic organisms have shown promise in treating diseases. Previously, we have reported on the efficacy of microencapsulated Lactobacillus reuteri NCIMB 30242 in a yogurt formulation at lowering serum cholesterol levels in otherwise healthy hypercholesterolemic adults. This study investigates the safety and toxicology of oral ingestion of microencapsulated L. reuteri NCIMB 30242 in a yogurt formulation. A randomized group of 120 subjects received a dose of 5 × 10¹⁰ CFU microencapsulated L. reuteri NCIMB 30242 in yogurt (n = 59) or placebo yogurt (n = 61) twice/day for 6 weeks. Clinical chemistry and hematological parameters of safety were analyzed. Fecal samples were collected at these time points for the analysis of deconjugated bile acids. The frequency, duration and intensity of adverse events (AEs) and clinical significance of safety parameters were recorded for both groups. No clinically significant differences between the probiotic yogurt and placebo yogurt treated groups were detected in either the blood clinical chemistry or hematology results and there was no significant increase in fecal deconjugated bile acids (P > 0.05) between treated and control groups. The frequency and intensity of AEs was similar in the two groups. These results demonstrate the safe use of this formulation in food.     

A randomized, controlled trial of vicarious experience through peer support for male first-time cardiac surgery patients: impact on anxiety, self-efficacy expectation, and self-reported activity

OBJECTIVES: The purpose of this study was to determine whether vicarious experience, in which former patients exemplify the active lives they are leading, reduces anxiety and increases self-efficacy expectation and self-reported activity in patients after cardiac surgery. DESIGN: A randomized, controlled trial was used to evaluate an intervention that linked volunteers who had recovered from cardiac surgery in dyadic support with patients about to undergo similar surgery. The linking was achieved by means of visits during the hospitalization and recovery period. SUBJECTS: Fifty-six first-time male patients undergoing coronary artery bypass graft (CABG) surgery, with a mean age of 56.5 years, were randomly assigned to an experimental (n = 27) or control group (n = 29). Outcome Measures: Anxiety was measured at 48 hours and 24 hours before surgery, and again at 5 days and 4 weeks after surgery. Self-efficacy expectation and self-reported activity were both evaluated at 5 days and 4 weeks after surgery. RESULTS: Only the experimental group showed a significant decrease in anxiety during hospitalization. At all measurement times after the first intervention, the experimental group reported significantly lower levels of anxiety compared with the control group. The experimental group reported significantly higher levels of self-efficacy expectation and self-reported activity for general activities, walking, and climbing stairs evaluated at 5 days, and for general activities at 4 weeks after surgery. CONCLUSIONS: Vicarious experience provided through dyadic support is effective in helping patients undergoing cardiac surgery cope with surgical anxiety and in improving self-efficacy expectations and self-reported activity after surgery. Dyadic support is a valuable tool for recovery from cardiac surgery that needs to be maintained and explored through nursing practice and research.