Carbetocin versus oxytocin for prevention of postpartum hemorrhage in obese nulliparous women undergoing emergency cesarean delivery

Objective: To assess and compare the effectiveness and safety of single IV polus dose of carbetocin, versus IV oxytocin infusion in the prevention of PPH in obese nulliparous women undergoing emergency Cesarean Delivery.

Methods: A double-blinded randomized-controlled trial was conducted on 180 pregnant women with BMI >30. Women were randomized to receive either oxytocin or carbetocin during C.S. The primary outcome measure was major primary PPH >1000?ml within 24?h of delivery as per the definition of PPH by the World Health Organization Secondary outcome measures were hemoglobin and hematocrit changes pre- and post-delivery, use of further ecobolics, uterine tone 2 and 12-h postpartum and adverse effects.

Results: A significant difference in the amount of estimated blood loss or the incidence of primary postpartum haemorrhage (>1000?ml) in both groups. Haemoglobin levels before and 24-h postpartum was similar. None from the carbetocin group versus 71.5% in oxytocin group needed additional utrotonics (p?<?0.01). The uterine contractility was better in the carbetocin group at 2, and 12-h postpartum (p?<?0.05).

Conclusions: A single 100-µg IV carbetocin is more effective than IV oxytocin infusion for maintaining adequate uterine tone and preventing postpartum bleeding in obese nulliparous women undergoing emergency cesarean delivery, both has similar safety profile and minor hemodynamic effect.     

Cyclic straining of cell-seeded synthetic ligament scaffolds: development of apparatus and methodology

Cyclic tensile strains acting along a ligament implant are known to stimulate cells that colonize it to proliferate and to synthesize an extracellular matrix (ECM), which will then remodel and form a new ligament structure. However, this process of tissue induction is poorly understood. As a first step toward elucidating this process, we aimed to investigate the effect of cyclic tensile strain on the proliferation of, and possible ECM synthesis by, cells colonizing ligament scaffolds. Because there was no commercially available apparatus to undertake such investigation the objectives of this study were to develop an apparatus for the application of cyclic tensile strains on cell-seeded synthetic ligament scaffolds and to develop and validate (through preliminary data obtained using the apparatus) methodology for studying the effect of cyclic strain on cell proliferation. We designed a multi-station test apparatus that operated inside an incubator. It allowed the application of tensile cyclic strains of between 0.5% and 5% at a frequency of 1 Hz on cell-seeded polyester ligament scaffolds immersed in culture medium. Test stations with windows in their bases could be easily de-coupled from the apparatus. This allowed monitoring of cell proliferation and morphology, with inverted light microscopy, through the transparent glass bases of the culture wells. Preliminary experiments lasting for 1 day or 9 weeks examined the effect of selected aspects of the cyclic strain on proliferation of cells seeded onto ligament scaffolds. Tests lasting for 1 day showed that the application of cyclic tensile strain of 5% for 4 h increased cell proliferation 24% above that observed in unstrained controls (p < .05). Scanning electron microscopy data from tests lasting for 9 weeks demonstrated further the dependency of cell proliferation and possible ECM synthesis on the magnitude of the strain. The larger the amplitude, the greater was the coverage of the scaffold with cells and ECM. Transmission electron microscopy of the ECM observed at 9 weeks showed evidence of collagen fibrils aligned in the direction of load in strained scaffolds, whereas the tissue on the control scaffolds was random.     

Deformation and failure of cartilage in the tensile mode

The aim of this study was to visualize, at the ultrastructural level, the deformation and failure mechanism of cartilage matrix in the tensile mode. Full-thickness dumbbell-shaped specimens were prepared from adult bovines. There were two specimen groups; in the 'parallel' group the specimen axis was parallel to the split lines defining the preferential orientation of the collagen in the articular surface, and in the 'perpendicular' group the specimen axis was perpendicular to the split lines. Specimens were placed with the articular surface uppermost and subjected to a graded series of strain within individual mini-tension devices, while observed with stereomicroscopy and confocal laser scanning microscopy. Thereafter, the changes in the ultrastructure were observed with both scanning and transmission electron microscopy. The mechanism of cartilage failure in the tensile mode comprised the following stages, whether the strain was applied parallel or perpendicular to the split line. (1) At 0% strain a fibrillar meshwork within the articular surface was predominantly orientated in the direction of the split line. (2) As strain increased, the fibrillar meshwork became more orientated in the parallel group and reorientated in the perpendicular group in the direction of the applied strain. (3) After complete reorientation of the fibrillar meshwork in the direction of the applied strain, the initial sign of failure was rupture of the fibrillar meshwork within the articular surface. (4) Subsequently, the rupture rapidly propagated into the deeper layers. Greater strains were required for fibrillar reorientation and complete rupture in the 'perpendicular group' than in the parallel group.     

Evaluation of serum mesothelin in malignant and benign ovarian masses

Purpose

To evaluate the diagnostic accuracy of serum mesothelin levels in patients with ovarian masses in comparison to serum cancer antigen (CA) 125 levels.

Methods

This diagnostic accuracy study was conducted in a gynecological oncology unit at Ain Shams University Maternity hospital. Based on radiological and clinical findings, a total of 110 patients were consecutively recruited. Preoperative serum mesothelin levels were assessed using enzyme-linked immunosorbent assay (ELISA) technique, while CA125 levels were determined using electrochemiluminescence immunoassay. All patients underwent exploratory laparotomy. Preoperative serum levels of both markers were correlated to histopathological reports obtained from each patient.

Results

A total of 96 patients were finally analyzed. Of the included 96 patients, 58 (60.4 %) had a benign ovarian lesion, while 38 (39.6 %) had a malignant lesion. The median serum CA125 levels were significantly higher in patients with malignant ovarian lesions than in patients with benign ovarian lesions [335.5 mIU/mL (range 60–1,127 mIU/mL) versus 33.65 mIU/mL (range 10.36–174 mIU/mL), P < 0.001]. The median serum mesothelin level was significantly higher in patients with malignant ovarian lesions than in patients with benign ovarian lesions [104.1 nmol/L (range 6.5–215.4 nmol/L) versus 12.65 nmol/L (range 6.5–102 nmol/L), P < 0.001]. The diagnostic sensitivity and specificity for mesothelin and CA125 were 97.4 and 98.3 % and 97.4 and 56.9 %, respectively. The combination of mesothelin with CA125 did not add predictive value to mesothelin compared with mesothelin alone [same sensitivity (97.4 %) and same specificity (98.3 %)]. Serum mesothelin levels rather than serum CA125 levels were a significant predictor of early-stage ovarian malignancy [Area under the curve = 0.732, 95 % confidence interval (0.543–0.921), P = 0.031].

Conclusion

In ovarian cancer, mesothelin seemed to have the same sensitivity, but a higher specificity than CA125. Combination of mesothelin and CA125 had no advantage over mesothelin alone. Mesothelin rather than CA125 was a significant predictor of early-stage ovarian cancer (stage I/II).     

Effect of cyclic tensile strain on proliferation of synovial cells seeded onto synthetic ligament scaffolds--an in vitro simulation

OBJECTIVE: Cyclic tensile strain is pivotal to the remodeling of tissue induced in implants used in reconstruction of anterior cruciate ligaments whether these implants were of autogenous tissues or synthetic materials. However, this process is poorly understood. The objective of this study was to investigate the short and medium-term effect of cyclic tensile strain on the proliferation of synovial cells seeded on ligament scaffolds. METHODS: 206 ligament scaffolds made from plasma treated polyester with an ultimate tensile strength of 320 N were used in this study. Synovial cells were obtained from the metatarsophalangeal joints of 2 years old bovines. After expansion of these, they were seeded onto the scaffolds which were subjected, in a specialized apparatus, to a cyclic tensile strain of 4.5% at a frequency of 1 Hz. Initially, the strain was applied for a period of 4 h, which was subsequently reduced in further experiments to 1.0 h and 0.5 h. In further tests, strains of approximately 2.5%, 1% and 0.6% were applied for 1 h at the same frequency. In all the above tests, which were short-term tests (lasting for approximately 1 day), cell proliferation was investigated by the uptake of thymidine with which cells were labeled according to prescribed protocols. Cell proliferation was further examined with light microscopy after 5 weeks and the degree of fill of inter-yarn spaces was quantified for strain amplitudes of 1, 2.5 and 4.5%. Equal number of control (not strained) specimens was used at each time point. RESULTS: In the 1-day experiments, for all durations of application of cyclic strain (exercise), the effect of strain on cell proliferation was inhibitory during the period of exercise and up to 18 h from its commencement, but was stimulatory 22-24 h afterwards. This stimulatory effect was maximal at an exercise period of 1 h. The study has also shown that there is a threshold for the amplitude of the strain (1%), at and below which cell proliferation was not significantly different from that observed in control specimens (P was <0.05 for all data). After 5 weeks of cyclic strain application, it was shown that the higher the amplitude of strain the larger was the area occupied by cells of the intra-yarn space. CONCLUSION: Both the amplitude of cyclic strain and duration of its application affect the proliferation of synovial cells seeded on ligament scaffolds. The data should be useful when selecting or designing an implant, and when prescribing a postoperative exercise regime.     

Autoantibodies to neutrophil cytoplasmic antigens (ANCA) do not bind to polymorphonuclear neutrophils in blood

BACKGROUND: Autoantibodies to neutrophil cytoplasmic antigens (ANCA), particularly to proteinase 3 (PR3), are found in the majority of patients with systemic Wegener's granulomatosis. The autoantibodies are widely used as diagnostic markers. Their role in the development and progression of the disease, however, is still under investigation. The primary target of ANCA, PR3, is located in the cytoplasm of polymorphonuclear neutrophils (PMN) or monocytes and is translocated to the cell surface upon stimulation. In patients with Wegener's granulomatosis PR3 is up-regulated most prominently during active disease. Despite the fact that both autoantibodies to PR3 and PMN expressing PR3 are present in patients with Wegener's granulomatosis, there is no evidence for binding of the autoantibodies to PMN. The present study was designed to analyze binding characteristics of autoantibodies to PR3 on PMN. METHODS AND RESULTS: PMN of patients with active Wegener's granulomatosis (N= 10) were tested for autoantibody binding. Despite high autoantibody titer and PR3 expression on the PMN, no surface-bound IgG was found on PMN ex vivo. When ANCA-containing plasma from patients was incubated with isolated PMN, stimulated to express PR3, again no specific binding of the autoantibody could be detected. Also keeping the samples on ice did not allow surface detection of IgG, ruling out degradation or internalization of the autoantibodies. Only when purified IgG fractions were used, binding to PMN was seen in 14 of 25 patients. Already 1% of plasma, however, was sufficient to greatly reduce the IgG binding. Reduced binding of the IgG fraction was also seen when a larger reaction volume was used. CONCLUSION: Our data indicate that autoantibodies to PR3 have a rather low affinity for surface-associated PR3 on PMN. This, in turn, argues against the hypothesis that ANCA contributes to the pathogenesis of the disease by stimulating viable PMN in whole blood.     

α‐Substitution Effects on the Ease of S→N‐Acyl Transfer in Aminothioesters

In S‐acylcysteines and homocysteines, the efficacy and rate of S→N‐acyl transfer (5 and 6 cyclic TSs) vary with the size of S‐acyl group. Conformational and quantum chemical calculations indicate that the spatial distance, b(N‐C), between the terminal amine and the thioester carbon is shortened by α‐C(O)X (X = OH, OMe, NH₂) substituents.     

The effect of timing of maternal tetanus,diphtheria, and acellular pertussis (Tdap) immunization during pregnancy on newborn pertussis antibody levels – A prospective study

Background

The Centers for Disease Control and Prevention recommend Tdap immunization during pregnancy, preferably at 27–36 weeks.

Aim

To ascertain whether there is a preferential period of maternal Tdap immunization during pregnancy that provides the highest concentration of pertussis-specific antibodies to the newborn.

Methods

This prospective study measured pertussis-specific antibodies in paired maternal-cord sera of women immunized with Tdap after the 20th week of their pregnancy (n = 61).

Results

The geometric mean concentrations (GMCs) of Immunoglobulin G (IgG) to pertussis toxin (PT) were higher in the newborns’ cord sera when women were immunized at 27–30⁺⁶ weeks (n = 21) compared with 31–36 weeks (n = 30) and >36 weeks (n = 7), 46.04 international units/milliliter (IU/mL) (95% CI, 24.29–87.30) vs. 8.69 IU/mL (95% CI, 3.66–20.63) and 21.12 IU/mL (95% CI, 7.93–56.22), p < 0.02, respectively. The umbilical cord GMCs of IgG to filamentous hemagglutinin (FHA) were higher in the newborns’ cord sera when women were immunized at 27–30⁺⁶ weeks compared with 31–36 weeks and >36 weeks, 225.86 IU/mL (95% CI, 182.34–279.76) vs. 178.31 IU/mL (95% CI, 134.59–237.03) and 138.03 IU/mL (95% CI, 97.61–195.16), p < 0.02, respectively.

Conclusions

Immunization of pregnant women with Tdap between 27–30⁺⁶ weeks was associated with the highest umbilical cord GMCs of IgG to PT and FHA compared with immunization beyond 31 weeks gestation. Further research should be conducted to reaffirm these finding in order to promote an optimal pertussis controlling policy.