Assessment of the Antiviral Properties of Recombinant Porcine SP-D against Various Influenza A Viruses In Vitro

The emergence of influenza viruses resistant to existing classes of antiviral drugs raises concern and there is a need for novel antiviral agents that could be used therapeutically or prophylacticaly. Surfactant protein D (SP-D) belongs to the family of C-type lectins which are important effector molecules of the innate immune system with activity against bacteria and viruses, including influenza viruses. In the present study we evaluated the potential of recombinant porcine SP-D as an antiviral agent against influenza A viruses (IAVs) in vitro. To determine the range of antiviral activity, thirty IAVs of the subtypes H1N1, H3N2 and H5N1 that originated from birds, pigs and humans were selected and tested for their sensitivity to recombinant SP-D. Using these viruses it was shown by hemagglutination inhibition assay, that recombinant porcine SP-D was more potent than recombinant human SP-D and that especially higher order oligomeric forms of SP-D had the strongest antiviral activity. Porcine SP-D was active against a broad range of IAV strains and neutralized a variety of H1N1 and H3N2 IAVs, including 2009 pandemic H1N1 viruses. Using tissue sections of ferret and human trachea, we demonstrated that recombinant porcine SP-D prevented attachment of human seasonal H1N1 and H3N2 virus to receptors on epithelial cells of the upper respiratory tract. It was concluded that recombinant porcine SP-D holds promise as a novel antiviral agent against influenza and further development and evaluation in vivo seems warranted

Treatment of tubal pregnancy in the netherlands: an economic comparison of systemic methotrexate administration and laparoscopic salpingostomy

OBJECTIVE: This study was undertaken to compare from a societal perspective the costs of systemic methotrexate administration with those of laparoscopic salpingostomy for the treatment of patients with tubal pregnancy. STUDY DESIGN: An economic evaluation was set up in tandem with a multicenter randomized clinical trial that compared systemic methotrexate administration and laparoscopic salpingostomy for the treatment of 100 hemodynamically stable patients with laparoscopically confirmed unruptured tubal pregnancy. Data on resources used for treatment and lost production time were prospectively collected and costs of both treatments were calculated by multiplying actual expenses for resource units at a single center and resource unit use measured in all centers. Costs were originally calculated in Dutch guilders and converted to US dollars at a rate of 1.67 guilders/$1. RESULTS: Because clinical outcomes of the trial were equivalent for the 2 strategies a cost-minimization analysis was done. Mean total costs per patient were$5721 for systemic methotrexate administration and $4066 for laparoscopic salpingostomy, with a mean difference of$1655 (95% confidence interval, $906-$2414). Costs of systemic methotrexate administration were similar to those of salpingostomy for patients in whom the initial serum human chorionic gonadotropin concentration was 3000 IU/L. CONCLUSIONS: Although systemic methotrexate administration is safe and effective for the treatment of tubal pregnancy, it does not necessarily reduce costs. Systemic methotrexate therapy could reduce costs if administered to patients with low initial serum human chorionic gonadotropin concentrations without confirmatory laparoscop

Should patients who are suspected of having an ectopic pregnancy undergo physical examination?

OBJECTIVE: To determine whether physical examination is useful for patients with suspected ectopic pregnancy (EP) for whom transvaginal sonography is performed and serum hCG levels are measured. DESIGN: Prospective study. SETTING: Two large teaching hospitals. PATIENT(S): Three hundred eighty-two patients with suspected EP, based on a positive urine pregnancy test and the presence of abdominal pain, vaginal bleeding, or risk indicators. INTERVENTION(S): Abdominal examination, speculum inspection, and digital vaginal examination. MAIN OUTCOME MEASURE: A final diagnosis made by transvaginal sonography, serum hCG measurement, and, if necessary, confirmatory laparoscopy. RESULT(S): One hundred sixteen (30%) of the 382 patients had an EP. At external abdominal examination, rebound tenderness and muscular rigidity had likelihood ratios of 3.7 and 8.0, respectively. Findings at speculum inspection and digital vaginal examination had likelihood ratios between 0.33 and 2.4. Logistic regression analysis showed that the additional information provided by physical examination for the diagnosis of EP is limited compared with the information provided by transvaginal sonography and serum hCG measurement alone. CONCLUSION: On the basis of our results, we believe that vaginal digital examination for patients with suspected EP is unnecessar

Are gestational age and endometrial thickness alternatives for serum human chorionic gonadotropin as criteria for the diagnosis of ectopic pregnancy?

OBJECTIVE: To compare gestational age and endometrial stripe thickness measurement with serum hCG measurement as criteria for the diagnosis of ectopic pregnancy (EP). DESIGN: Prospective study. SETTING: Two large teaching hospitals in Amsterdam, The Netherlands. PATIENT(S): Three hundred fifty-four consecutively seen pregnant patients who presented between September 1993 and April 1996 with suspected EP and in whom transvaginal ultrasonogram showed no intrauterine pregnancy or EP. Ultrasonography was performed by one of the study investigators or, during shifts, by the resident on call. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The accuracy of gestational age, endometrial stripe thickness, and serum hCG measurement in the diagnosis of EP was evaluated with receiver operating characteristic curve analysis. RESULT(S): Gestational age and endometrial stripe thickness could not discriminate between patients with EP and patients without EP, whereas serum hCG had an acceptable area under the receiver operating characteristic curve. CONCLUSION(S): Gestational age and endometrial thickness are not useful in the diagnosis of EP. Serum hCG measurement is the diagnostic instrument of choice in patients with suspected EP when transvaginal ultrasonography does not reveal a diagnosi

Non-invasive management of patients with suspected ectopic pregnancy: a survey among Dutch gynaecologists

OBJECTIVE: To investigate if implementation of a non-invasive diagnostic work up of patients with suspected ectopic pregnancy, involving transvaginal sonography and serum human chorionic gonadotrophin (hCG) measurement decreases the likelihood of performing diagnostic laparoscopies. STUDY DESIGN: We interviewed 27 Dutch gynaecologists using 16 structured case summaries in a fractional factorial design. Each case summary concerned a hypothetical patient with suspected ectopic pregnancy. For each case presentation, the gynaecologists were asked for their inclination to perform laparoscopy. RESULTS: There were substantial differences in the degree to which data from a non-invasive work-up influenced the decision to perform a laparoscopy. Some gynaecologists would perform laparoscopy in all 16 patients at the first visit, whereas others would initially admit none of them. CONCLUSION: Dutch gynaecologists seem to be familiar with a non-invasive diagnostic approach in women with suspected ectopic pregnancy. However, there are considerable differences in management approach probably due to individual variability in weighing the risks and benefits of expectant managemen

Can noninvasive diagnostic tools predict tubal rupture or active bleeding in patients with tubal pregnancy?

OBJECTIVE: To evaluate the ability of noninvasive diagnostic tools to predict tubal rupture and active bleeding in patients with tubal pregnancy. DESIGN: Prospective cohort study. SETTING: Two large teaching hospitals in Amsterdam, The Netherlands. PATIENT(S): Consecutively seen patients with suspected tubal pregnancy who were scheduled to undergo confirmative laparoscopy. MAIN OUTCOME MEASURE(S): Tubal rupture and/or active bleeding confirmed at laparoscopy. RESULT(S): Sixty-five (23%) of 288 patients had tubal rupture and/or active bleeding at laparoscopy. Abdominal pain, rebound tenderness on abdominal examination, fluid in the pouch of Douglas at transvaginal ultrasound examination, and a low serum hemoglobin level were independent predictors of tubal rupture and/or active bleeding. Pregnancy achieved with the use of IVF-ET and the presence of an ectopic gestational sac or an ectopic mass at ultrasound examination reduced the risk of tubal rupture. Abdominal pain was the most sensitive predictor, with a sensitivity of 95%. CONCLUSION(S): Because the nonsurgical management of tubal pregnancy should be used only when the risk of tubal rupture and/or active bleeding is low, it can be safely applied in only a limited number of patient

Serum human chorionic gonadotropin measurement in the diagnosis of ectopic pregnancy when transvaginal sonography is inconclusive

OBJECTIVE: To assess the accuracy of initial and repeated serum hCG measurements in the diagnosis of ectopic pregnancy (EP) in patients in whom transvaginal sonography is inconclusive and to evaluate whether patient characteristics influence the accuracy of serum hCG measurements. DESIGN: Prospective study. SETTING: Two large teaching hospitals in Amsterdam, the Netherlands. PATIENT(S): Three hundred fifty-four consecutively seen pregnant patients with suspected EP and inconclusive transvaginal sonographic findings. INTERVENTION(S): Serum hCG measurements. MAIN OUTCOME MEASURE(S): The performance of repeated serum hCG measurements in the diagnosis of EP was evaluated through the analysis of receiver operating characteristic curves. RESULT(S): Initial serum hCG measurements were more diagnostic in conjunction with sonographic evidence of an ectopic mass or fluid in the pouch of Douglas than in the absence of sonographic abnormalities. On repeated measurement, the course of the serum hCG concentration provided more diagnostic information than did the absolute serum hCG concentration 2 and 4 days after the start of the diagnostic process. CONCLUSION(S): The interpretation of serum hCG measurements should depend on additional findings at transvaginal sonography. A cutoff level of 1,500 IU/L is recommended for patients with an ectopic mass or fluid in the pouch of Douglas; in patients without these findings, the cutoff level should be at least 2,000 IU/L. Four days after the start of the diagnostic process, any rise in the serum hCG concentration makes the diagnosis of EP very likel