Antenatal detection of arterio-arterial anastomoses by Doppler placental assessment in monochorionic twin pregnancies

OBJECTIVES: To evaluate the reproducibility of Doppler antenatal detection of arterio-arterial anastomoses (AAA) in monochorionic (MC) twin pregnancies. METHODS: Between October 2002 and February 2004, 21 MC diamniotic twin pregnancies and one dichorionic triamniotic triplet seen at the Twin Clinic at the University of Brescia were recruited. After routine ultrasonographic assessment, AAA were searched using Color or Power and spectral Doppler. The presence of AAA was confirmed postnatally by placental injection studies. RESULTS: Data of 19 patients were available for the analysis. AAA were detected in 12 cases (63%) antenatally and in 16 (84.2%) at injection study. Sensitivity and specificity of Doppler for detecting AAA were 75 and 100%, respectively. Detection rates increased at advanced gestations and with anterior/fundal placentae. The incidence of twin-twin transfusion syndrome was higher in the group with no AAA detected in vivo compared to the group with AAA found with Doppler (28.5 vs. 16.6%), but the difference was not statistically significant (p = 0.5). CONCLUSION: This study confirmed the feasibility of AAA Doppler detection in vivo in MC pregnancies.     

Polar body morphology and spindle imaging as predictors of oocyte quality

It has been suggested that first polar body (PBI) morphology reflects oocyte competence. Oocytes with an intact normal-sized PBI have been described as generating better day 2 embryos, higher blastocyst yield, and increased pregnancy and implantation rates. In other studies, PBI morphology was found to be unrelated to fertilization rate, embryo quality, and blastocyst formation. In a prospective analysis, the predictive value of the PBI was investigated by comparing the development of oocytes retrieved from intracytoplasmic sperm injection patients and displaying different PBI morphology, classified according to the following characteristics: normal size and smooth surface (I), fragmented (II), rough surface (III), or large size (IV). Fertilization rates were 59, 57, 64 and 60% respectively. No significant differences were found between the various groups. The proportions of high quality (grade A) day 2 embryos were also comparable among groups I-III (14, 12 and 17% respectively), while the low number of grade A embryos in group IV (two embryos) did not allow comparison with the other classes. These data do not suggest that PBI selection can contribute to identification of embryos with high developmental ability. In order to establish alternative criteria for oocyte selection, a metaphase II (MII) spindle analysis was also conducted via Polscope. In oocytes of patients of different age, spindle retardance (which reflects the high order and density of microtubules) was compared with parameters of embryo development. In aged patients, a trend was observed between low retardance and poor embryo quality, although in general the association between retardance and oocyte developmental performance did not reach statistical significance.     

Jelly beans as an alternative to a cola beverage containing fifty grams of glucose

OBJECTIVE: Our purpose was to test the diagnostic value and patient tolerance of jelly beans as an alternative to a 50 gm glucose solution.STUDY DESIGN: Pregnant women between 26 to 30 weeks of gestation confirmed by early ultrasonography were recruited to participate in the study. Each participant was given a cola beverage containing 50 gm of glucose. The plasma glucose level was determined 1 hour later. Within 2 weeks of the 50 gm glucose test, each patient ate 18 jelly beans and had her plasma glucose level tested after 1 hour. Finally, within 2 weeks of the jelly bean test a 100 gm, 3-hour glucose tolerance test was performed on each subject. The results of the 3-hour test were used to define the presence of absence of gestational diabetes and carbohydrate intolerance by the criteria of The American College of Obstetricians and Gynecologists. Patient tolerance was rated by responses to questions regarding side effects.RESULTS: One bundred fifty-seven women completed the study. the mean maternal age, gravidity, parity, and number of abortions were 26.06 years, 2.66, 0.96, and 0.69. By use of a 140 mg/dl threshold, the sensitivity, specificity, and positive predictive value of the cola beverage was 46%, 81%, and 18%. These values at a 120 mg/dl threshold for jelly beans were 54%, 81%, and 20%, respectively. The patient tolerance was greater for the jelly beans compared with the 50 gm cola beverage.CONCLUSION: Jelly beans may serve as an alternative to a cola beverage containing 50 gm of glucose.     

Development and characterization of biodegradable nanospheres as delivery systems of anti-ischemic adenosine derivatives

We report a preliminary study concerning the encapsulation modalities in nanoparticles of the anti-ischemic drug N6-cyclopentyladenosine (CPA) and its pro-drug 5'-octanoyl-CPA (Oct-CPA). The release of these compounds and the related pro-drug stability effects in human whole blood have been tested. Moreover, the influence of the delivery systems on CPA interaction toward human adenosine A1 receptor has been analysed. The nanospheres were prepared by nanoprecipitation or double emulsion solvent evaporation method using poly(lactic acid) and recovered by gel filtration or ultracentrifugation or dialysis. Free and encapsulated Oct-CPA was incubated in fresh blood and its stability was analysed with HPLC. Quite spherical nanoparticles with mean diameters ranging between 210+/-50 and 390+/-90 nm were obtained. No encapsulation occurred when CPA was used. Satisfactory results concerning drug content (0.1-1.1% w/w) and encapsulation efficiency (6-56%) were achieved when Oct-CPA was employed. The controlled release of the pro-drug was achieved, being released within a range of 1-4 h, or very slowly, depending on nanoparticle preparations. The hydrolysis rate of Oct-CPA in human whole blood appeared stabilized in human whole blood with modalities related to the release patterns. The presence of all nanoparticle preparations did not interfere with CPA interaction at its action site.     

Detection of herpesvirus-6A in a case of subacute cerebellitis and myoclonic dystonia

This is a case study of a child who developed roseola infantum first, then varicella, and was later affected by acute cerebellar syndrome, severe truncal ataxia, and myoclonic dystonia. Human herpesvirus 6 (HHV-6) A and B were detected in the cerebrospinal fluid (CSF) and peripheral blood, respectively, upon ataxia onset. The intricacy of this case suggests multifaceted conclusions ranging from the need for a multidirectional approach to neurological diseases, to confirmation of a more pronounced neurotropism of HHV-6A and a possible role of viruses in myoclonic dystonia syndrome, although this last hypothesis should be confirmed by larger studies.     

A systematic review of currently available pharmacological neuroprotective agents as a sole intervention before anticipated or induced cardiac arrest

We conducted a Medline search for controlled studies evaluating currently available drugs for pharmacological neuroprotection. They had to be administered prior to transient global cerebral ischaemia without further non-pharmacological measures. We deliberately excluded focal ischaemia since its pathophysiology is substantially different from global ischaemia. A total of 45 articles conducted exclusively in laboratory animals met these criteria. The following classes of agents were evaluated: anaesthetics, GABAergic drugs, calcium-antagonists, anticonvulsives, sodium-channel blockers, potassium-channel activators, NMDA-receptor antagonists, hormones, vasodilators, dopamine- and alpha2-agonists, magnesium, xanthine oxidase- and cyclooxygenase inhibitors, a nootropic, a protease inhibitor, and immunosuppressants. Some of them were applied chronically and others administered via clinically impracticable routes. The available literature favours isoflurane, phenytoin, lamotrigine, magnesium, and potentially, nimodipine, and flunarizine. If factors like costs, toxicity, side effects, route and mode of application are considered, isoflurane and MgSO4 that have also been safely applied to patients with compromised left ventricular pump function are advantageous but their true role in human neuroprotection remains unclear.     

TRAIL counteracts the proadhesive activity of inflammatory cytokines in endothelial cells by down-modulating CCL8 and CXCL10 chemokine expression and release

Exposure of endothelial cells to recombinant tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induced a modest (2-fold) increase of HL-60 cell adhesion as compared to TNF-alpha (40-fold) or interleukin 1beta (IL-1beta; 20-fold). However, pretreatment of endothelial cultures with TRAIL determined a significant reduction of the proadhesive activity induced by both TNF-alpha and IL-1beta. Unexpectedly, the antiadhesive activity of TRAIL was not due to interference with the nuclear factor kappaB (NF-kappaB)-mediated up-regulation of surface intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin adhesion molecules in response to inflammatory cytokines. In searching for the molecular mechanism underlying this biologic activity of TRAIL, a cDNA microarray analysis was performed. TRAIL pretreatment variably down-modulated the mRNA steady-state levels of several TNF-alpha-induced chemokines, and, in particular, it abrogated the TNF-alpha-mediated up-regulation of CCL8 and CXCL10. Of note, the addition of optimal concentrations of recombinant CCL8 plus CXCL10 to endothelial cultures completely restored the proadhesive activity of TNF-alpha. Moreover, experiments performed with agonistic anti-TRAIL receptor antibodies demonstrated that both TRAIL-R1 and TRAIL-R2 contributed, although at different levels, to TRAIL-induced chemokine modulation. Taken together, our data suggest that TRAIL might play an important role in modulating leukocyte/endothelial cell adhesion by selectively down-regulating CCL8 and CXCL10 chemokines.     

Urinary bladder partial carbon dioxide tension during hemorrhagic shock and reperfusion: an observational study

Introduction

Continuous monitoring of bladder partial carbon dioxide tension (PCO₂) using fibreoptic sensor technology may represent a useful means by which tissue perfusion may be monitored. In addition, its changes might parallel tonometric gut PCO₂. Our hypothesis was that bladder PCO₂, measured using saline tonometry, will be similar to ileal PCO₂ during ischaemia and reperfusion.

Method

Six anaesthetized and mechanically ventilated sheep were bled to a mean arterial blood pressure of 40 mmHg for 30 min (ischaemia). Then, blood was reinfused and measurements were repeated at 30 and 60 min (reperfusion). We measured systemic and gut oxygen delivery and consumption, lactate and various PCO₂ gradients (urinary bladder–arterial, ileal–arterial, mixed venous–arterial and mesenteric venous–arterial). Both bladder and ileal PCO₂ were measured using saline tonometry.

Results

After bleeding systemic and intestinal oxygen supply dependency and lactic acidosis ensued, along with elevations in PCO₂ gradients when compared with baseline values (all values in mmHg; bladder ΔPCO₂ 3 ± 3 versus 12 ± 5, ileal ΔPCO₂ 9 ± 5 versus 29 ± 16, mixed venous–arterial PCO₂ 5 ± 1 versus 13 ± 4, and mesenteric venous–arterial PCO₂ 4 ± 2 versus 14 ± 4; P < 0.05 versus basal for all). After blood reinfusion, PCO₂ gradients returned to basal values except for bladder ΔPCO₂, which remained at ischaemic levels (13 ± 7 mmHg).

Conclusion

Tissue and venous hypercapnia are ubiquitous events during low flow states. Tonometric bladder PCO₂ might be a useful indicator of tissue hypoperfusion. In addition, the observed persistence of bladder hypercapnia after blood reinfusion may identify a territory that is more susceptible to reperfusion injury. The greatest increase in PCO₂ gradients occurred in gut mucosa. Moreover, the fact that ileal ΔPCO₂ was greater than the mesenteric venous–arterial PCO₂ suggests that tonometrically measured PCO₂ reflects mucosal rather than transmural PCO₂. Ileal ΔPCO₂ appears to be the more sensitive marker of ischaemia.