Ketanserin in pre-eclamptic patients: transplacental transmission and disposition in neonates

The aim of this prospective, observational study was to assess transplacental transmission of ketanserin, an antihypertensive drug used in pre-eclampsia, and to determine disposition and effects in the neonate after maternal ketanserin use. In 22 pregnant women with severe pre-eclampsia, admitted to the antenatal ward in the period 1999-2001, the ratio of drug levels in the umbilical cord to drug levels in maternal blood just before delivery was used as an indicator of placental transmission. Disposition of ketanserin was assessed using neonatal plasma concentrations of ketanserin in eight neonates after birth. A median placental transmission was found in the pre-eclamptic women of 0.95 (0.612-1.24) for ketanserin and for its metabolite, ketanserinol, of 0.60 (0.5-0.77). Pharmacologically relevant concentrations of ketanserin were found in the neonate after delivery. The elimination half-life of ketanserin in the neonate varied between 12.7 and 43.7 hours (median 19.3 hours) and of ketanserinol between 13.8 and 34.4 hours (median 18.7 hours). Despite the high placental transmission and disposition in the neonate, no apparent adverse effects in the neonates could be detected. In conclusion, a high placental transmission of ketanserin and its metabolite ketanserinol occurred after maternal treatment of pre-eclampsia with ketanserin and pharmacologically active concentrations of ketanserin are found in the neonate for a prolonged period after delivery.     

Assessment of macro‐ and microcirculation in contemporary critical limb ischemia

Objectives : A paucity of data exists regarding manifestations of macro‐ and microcirculation in contemporary critical limb ischemia (CLI). The aim of this study was (1) to evaluate the differences in foot circulation based on angiographic findings, (2) to clarify the relationship between macro‐ and microcirculation, and (3) to investigate the effects of postural changes on micro as well as macrocirculation between the supine position to the dependent position. Methods : A total of 40 critically ischemic limbs in 29 patients were included in this study. Noninvasive evaluation of macrocirculation, based on the ankle brachial index (ABI) and ankle pressure, and microcirculation, using skin perfusion pressure (SPP), was performed in both the supine and dependent positions. Results : There was no significant difference in macro‐ and microcirculations between any angiographical involvements. In the supine position, dorsal SPP correlated significantly with ABI (P = 0.021, r = 0.363) and ankle‐pressure (P = 0.001, r = 0.495), whereas plantar SPP failed to correlate with ABI (P = 0.198, r = 0.208) or ankle‐pressure (P = 0.185, r = 0.214). In the dependent position, however, SPP showed no significant correlation with ABI and ankle pressure. Postural change from the supine to dependent position yielded a significant increase in SPP (dorsal: 37.2 ± 16.2 to 77.9 ± 17.7 mm Hg, P < 0.001; plantar: 33.6 ± 17.3 to 75.7 ± 18.3 mm Hg, P < 0.001) as well as ABI and ankle‐pressure (ABI: 0.70 ± 0.35 to 0.78 ± 0.42, P = 0.003; ankle‐pressure; 108 ± 61 to 111 ± 60 mm Hg, P = 0.038). The effect of postural change on SPP showed no difference between patients with and without any clinical and angiographical complications. Conclusions : Of microcirculation assessed, only dorsal SPP correlated significantly with macrocirculation in the supine position. Furthermore, postural change from the supine to dependent position produced a dramatic improvement in microcirculation due to the effects of gravity. © 2011 Wiley Periodicals, Inc.     

Bradykinin and angiotensin-converting enzyme inhibition in cardioprotection

OBJECTIVES:

To show that angiotensin-converting enzyme (ACE) inhibition potentiates subthreshold ischemic preconditioning (IPC) via the elevation of bradykinin activity, leading to a fully delayed cardioprotective response.

METHODS:

On day 1 of the experiment, pigs were subjected to sham (group 1, controls) or IPC protocols. In groups 2 and 3, 4×5 min and 2×2 min of IPC, respectively, were elicited by occluding the left anterior descending coronary artery with percutaneous transluminal coronary angioplasty inflatable balloon catheter. Group 4 was subjected to the ACE inhibitor perindoprilate only. In group 5, the pigs were pretreated with perindoprilate (0.06 mg/kg) and then subjected to 2×2 min IPC. In group 6, intracoronary HOE 140 (a selective bradykinin B₂ receptor antagonist) was added before the perindoprilateaugmented subthreshold (2×2 min) PC stimulus. On the second day, all animals underwent 40 min left anterior descending coronary artery ligation and 3 h reperfusion, followed by infarct size analysis using triphenyl tetrazolium chloride staining.

RESULTS:

The rates of infarct size and risk zone were the following in the experimental groups: group 1, 42.8%; group 2,19.5% (P<0.05); group 3, ischemia/reperfusion (I/R) 33.4%; group 4, I/R 18.4% (P<0.05); group 5, I/R 31.2%; and group 6, I/R 36.3%. A significant increase of nuclear factor kappa B activation in groups 2 and 4 was seen.

CONCLUSIONS:

Results confirm that ACE inhibitors do not give total pharmacological IPC, but they enhance the induction effect of small ischemic insults, which raises the ischemic tolerance of myocardium. It was determined that enhanced bradykinin activity leads to downstream nuclear factor kappa B activation in this model.     

Trimethoprim‐induced immune hemolytic anemia in a pediatric oncology patient presenting as an acute hemolytic transfusion reaction

A 10‐year‐old male with acute leukemia presented with post‐chemotherapy anemia. During red cell transfusion, he developed hemoglobinuria. Transfusion reaction workup was negative. Drug‐induced immune hemolytic anemia was suspected because of positive direct antiglobulin test, negative eluate, and microspherocytes on smear pre‐ and post‐transfusion. Drug studies using the indirect antiglobulin test were strongly positive with trimethoprim and trimethoprim–sulfamethoxazole but negative with sulfamethoxazole. The patient recovered after discontinuing the drug, with no recurrence in 2 years. Other causes of anemia should be considered in patients with worse‐than‐expected anemia after chemotherapy. Furthermore, hemolysis during transfusion is not always a transfusion reaction. Pediatr Blood Cancer. 2010;55:1201–1203. © 2010 Wiley‐Liss, Inc.     

Congenital chylothorax: from foetal life to adolescence

Aim: To analyse the main prenatal and postnatal features of congenital chylothorax (CC), and the outcome including mid‐term follow‐up. Methods: We searched our databases for CC diagnosed between 1990 and 2006. Data of 29 cases were retrieved and analysed. Follow‐up until 3 years of age was available for all patients. Results: Most patients were diagnosed prenatally (94%) and most cases were complicated by foetal hydrops (66.7%). The overall survival rate at 3 years was 56%. A significantly poorer outcome was observed when foetal hydrops, preterm birth < 34 weeks, large effusions and/or early‐onset pneumothorax were present. An important but not significant improvement in the survival rate was observed through the study period; while in 1990–1998, the survival rate was 41.7%, from 1999 to 2006 it was 66.7% (p = 0.19). In the mid‐term follow‐up, we did not observe any recurrence of CC and most infants remain asymptomatic. However, 27% of survivors were diagnosed as having asthma in early infancy. Conclusion: CC still carries a significant risk of perinatal mortality. However, continuous advances in foetal and neonatal medicine are improving the prognosis of these patients, and nowadays most of them are likely to survive. Beyond the neonatal period, most survivors have an uneventful outcome.     

Confirmation of high blood flow rates through 150 μ filter/high-flow tubing

Many new products designed to assist in rapid blood infusion are appearing. Some highly touted and routinely used devices for intravenous (IV) infusion have recently been shown to be, at least in part, defective. A tubing with an in-line 150 μ filter (150 μ High-Flow Blood Filter; Saftifllter^® Blood Administration Sets; Cutter Biological, Berkeley, CA 94710) has recently been introduced to facilitate rapid blood transfusion. It is claimed that at least 8.5 units of blood can be rapidly run through each set before replacement is necessary. To test this under simulated clinical conditions, four sets of ten random units of outdated erythrocytes at 4 to 9°C were each admixed with 250 mL 70°C 0.9 NaCl and infused through the system under a constant 300 mmHg pressure. Two sets infused through unmodified tubing flowed at an average of 25 mL/sec (1500 mL/min) before there was an appreciable slowing of the flow rate. Two sets with 8 Fr catheters attached infused at an average of 22 mL/sec (1320 mL/min) before there was an appreciable slowing of the flow rate. Even after the flow slowed, the 9th and 10th units infused at an average greater than 10 mL/sec (600 ml/min). The tubing/filter exceeded the manufacturer's published claims. This tubing/filter appears to be one element that could be an effective component of a high-flow infusion system.     

Transient synovitis of the hip in children: role of US

Transient synovitis of the hip remains a common diagnostic problem for the clinician. The physical signs are not pathognomonic of the condition, and the classic technical examinations are of little help. Therefore, the authors retrospectively studied the value of hip arthrosonography in 46 children with clinical symptoms suggesting pathologic hip conditions. In 20 of the 21 patients with a final diagnosis of transient synovitis, articular effusion was detected on ultrasound (US). Conventional radiography showed an increased medial joint space in only eight of these patients. Increased echogenicity of the articular fluid was found in both transient synovitis and septic arthritis. The high sensitivity of US in detecting intraarticular fluid was demonstrated by cadaver studies.     

The impact of a quadrivalent human papillomavirus (types 6, 11, 16, 18) virus-like particle vaccine in European women aged 16 to 24

Background  Quadrivalent human papillomavirus (HPV types 6/11/16/18) L1 VLP vaccine is highly effective in preventing HPV 6/11/16/18-related cervical and external genital disease. Herein, we evaluated the impact of the quadrivalent HPV 6/11/16/18 L1 VLP vaccine on prevention of HPV-associated cervico-genital lesions in a broad population of sexually active European women.
Methods  Female subjects ( N = 9265) aged 16–24 with four or fewer lifetime sexual partners were enrolled and randomized to quadrivalent HPV vaccine or placebo. Subjects underwent cervicovaginal sampling for HPV DNA detection. Papanicolaou testing and anti-HPV 6/11/16/18 serology testing was also performed.
Results  Vaccine efficacy against lesions representing immediate cervical cancer precursors (cervical intraepithelial neoplasia grade 2/3 or adenocarcinoma in situ ) related to HPV 6/11/16/18 in the per-protocol population was 100.0%[95% confidence interval (95% CI), 89.8–100.0]. Efficacy against external genital lesions (vulvar or vaginal intraepithelial neoplasia, condyloma, vulvar or vaginal cancer) related to vaccine HPV types in the per-protocol European population was 99.0% (95% CI, 94.4–100.0).
Conclusion  These data demonstrate that quadrivalent HPV 6/11/16/18 vaccination programs in 16- to 24-year-old European women can be beneficial.
NCT0009252, NCT00092534, NCT00092495     

Assessment of baroreflex sensitivity in patients with preserved and impaired left ventricular function by means of the Valsalva manoeuvre and the phenylephrine test

The purpose of the present study was to assess the agreement between measurements of baroreflex sensitivity (BRS) obtained by the Valsalva manoeuvre and by the phenylephrine test in patients with previous myocardial infarction and different degrees of left ventricular dysfunction. Patients with a previous myocardial infarction were enrolled consecutively into two groups according to their left ventricular ejection fraction (LVEF): 40% (n=52). All patients underwent BRS assessment by the phenylephrine technique (Phe-BRS) and by the Valsalva manoeuvre, with the latter using both the overshoot part of phase IV (Ov-VM-BRS) and the whole of phase IV (IV-VM-BRS). The linear association between methods was assessed by correlation analysis and the agreement was evaluated by computing the bias and the limits of agreement. IV-VM-BRS and Ov-VM-BRS could not be computed in 26% and 39% of patients respectively. For both indices a much higher percentage of non-computable Valsalva manoeuvre slopes was found in the group of patients with LVEF 40% the results were: r=0.91 (P<0.001), bias=0.1 ms/mmHg (P=0.84) and limits of agreement from -4.8 to 5 ms/mmHg. When comparing Phe-BRS and IV-VM-BRS, we found r=0.67 (P=0.001), bias=-1.5 ms/mmHg (P=0.06) and limits of agreement from -8.8 to 5.7 ms/mmHg in the group of patients with LVEF 40%. Dichotomizing Ov-VM-BRS, the best cut-off value to identify patients with a Phe-BRS of <3 ms/mmHg was found to be 7 ms/mmHg, giving 100% sensitivity and 69% specificity. In conclusion, estimation of BRS by the Valsalva manoeuvre in post-myocardial infarction patients is limited by a large number of non-measurable results. When computable, measurements are well correlated with those obtained by Phe-BRS, but, because of large limits of agreement, the two methods cannot be used interchangeably. If used as a screening test for risk stratification, the Valsalva manoeuvre could reduce by about one-third the need for phenylephrine injection.