Targeting Telomerase with an HLA Class II-Restricted TCR for Cancer Immunotherapy

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Effects of sulfasalazine on lipid peroxidation and histologic liver damage in a rat model of obstructive jaundice and obstructive jaundice with lipopolysaccharide-induced sepsis

Background: Sulfasalazine, an inhibitor of cyclooxygenase, 5-lipoxygenase, and nuclear factor κB (NF-κB), has been found to alleviate oxidative damage, proinflammatory cytokine production, bile-duct proliferation, neutrophil infiltration, and fibrosis. Therefore, it may have a potential effect in attenuating lipid peroxidation and histologic liver damage in patients with biliary obstruction and biliary obstruction with sepsis.Objective: The aim of this study was to investigate the effect of sulfasalazine on lipid peroxidation and histologic liver damage due to obstructive jaundice (OJ) and to OJ with lipopolysaccharide (LPS)-induced sepsis in an experimental model.Methods: Male Wistar rats, weighing 150 to 220 g, were randomized into 6 groups: OJ; OJ + LPS; OJ + sulfasalazine; OJ + sulfasalazine + LPS (sulfasalazine administered before sepsis); OJ + LPS + sulfasalazine (sulfasalazine administered after sepsis); and sham. Liver malondialdehyde (MDA) and myeloperoxidase (MPO) activities were assessed to monitor lipid peroxidation and neutrophil infiltration in liver tissue. Histologic liver damage was evaluated with hematoxylin-eosin stained slides. Liver tissue NF-κB and caspase-3 expression were studied immunohistopathologically to evaluate lipid peroxidation, liver damage, and hepatocyte apoptosis.Results: Forty-eight rats were evenly randomized into 6 groups of 8. MDA (P = 0.001), MPO (P = 0.001), NF-κB (P = 0.003), caspase-3 expression (P = 0.002), and liver injury scores (P = 0.002) increased significantly in the OJ group compared with the sham group. Compared with the OJ group, MDA (P = 0.030) and MPO levels (P = 0.001), and liver injury scores (P = 0.033) were decreased significantly in the OJ + sulfasalazine group. In the OJ + sulfasalazine + LPS and OJ + LPS + sulfasalazine groups, MDA (P = 0.008 and P = 0.023, respectively) and MPO (both, P = 0.001) were significantly decreased; however, liver NF-κB, caspase-3 expression, and liver injury scores were not significantly different compared with the OJ + LPS group. There was no significant difference between the OJ + LPS + sulfasalazine and OJ + sulfasalazine + LPS groups in regard to all end points when comparing the effects of sulfasalazine administered before or after sepsis.Conclusions: Sulfasalazine was associated with decreased neutrophil accumulation and lipid peroxidation in these rats with OJ. Administration of sulfasalazine before or after LPS-induced sepsis was associated with a reduction in lipid peroxidation and neutrophil accumulation; however, it did not attenuate histologic liver damage. There was no difference between the findings when sulfasalazine was administered before or after sepsis in OJ.     

Does the diameter of an endometrioma predict the extent of pelvic adhesions associated with endometriosis?

OBJECTIVE: To correlate ovarian endometrioma diameter with the extent of pelvic adhesions. STUDY DESIGN: Forty women with unilateral ovarian cysts thought to be endometriomas were prospectively recruited. The interventions were transvaginal ultrasound to measure the size of the ovarian endometrioma and a laparoscopic surgical procedure, including detailed pelvic assessment. Main outcome measures were pelvic adhesion scores using the American Fertility Society revised classification of endometriosis. RESULTS: Thirty-two women met the inclusion criteria. Twelve had an endometrioma < 3 cm in diameter; 12, 3-5 cm; and 8, > 5 cm. Adhesion scores from various anatomic areas did not differ across these 3 groups. No correlation between the size of the endometrioma and associated pelvic adhesions was found using multiple regression analysis. CONCLUSION: The size of an endometrioma measured by transvaginal ultrasound does not correlate with the extent of adhesive disease. Small (< 3 cm) endometriomas may be associated with a considerable degree of pelvic adhesions.     

Fetal Doppler Hypoxic index for the prediction of abnormal fetal heart rate at delivery in chronic fetal distress

OBJECTIVE: To design a Doppler Hypoxic index (HI), which takes into account both the duration and the intensity of fetal flow redistribution (i.e. hypoxia) for predicting the occurrence of abnormal fetal heart rate (FHR) at delivery. METHOD: Sixty-six pregnancies with hypertension and/or growth retardation (IUGR) were investigated (age: 23+/-5 years; primigravidas: 30%, CS 59%; hospitalisation: 10+/-8 days, IUGR (<10 c) 82%, intensive care 23%, fetal death 1). Umbilical (URI) and cerebral (CRI) Doppler resistance indices, and the C/U ratio (CRI/URI) were measured every 2 days from admission to delivery. HI was calculated by summing the daily %C/U reduction (in % from normal cut-off limit 1.1) over the period of observation (or mean C/U reduction in % from 1.1 x number of days of observation). Doppler C/U and HI were compared with fetal heart rate (FHR) traces, and perinatal data. RESULTS: HI > 160% was associated with abnormal FHR in 80% of the cases (PPV = 87%, NPV = 88%). HI > 160% predicted the occurrence of abnormal FHR 8+/-6 days before they happened. CONCLUSION: A combination of intensity and duration of the fetal flow redistribution (i.e. hypoxia) evaluated by Doppler is correlated with the occurrence of abnormal fetal heart rate.     

Successful sleeve lobectomy of pediatric inflammatory myofibroblastic tumor

Inflammatory myofibroblastic tumor (IMT) is an uncommon solid tumor that was originally described in the lung. A 4‐year‐old girl was admitted to hospital with urticarial rash. On chest radiographs, an opacity was seen in the inferior zone of the left lung, and computed tomography showed a mass in the left lower lobe. Left lower sleeve lobectomy was performed, and the diagnosis was confirmed as IMT. Sleeve resection is the best option in lesions located in the mainstem bronchus or secondary carina. Herein, we present a rare case of IMT of the lung that was successfully treated with sleeve lobectomy. There have been fewer than 15 childhood cases of IMT reported in the literature, and the present 4‐year‐old patient is one of the youngest.     

Placebo-controlled randomized comparison of vaginal with rectal misoprostol in the prevention of postpartum hemorrhage

AIM: To compare vaginally administered misoprostol to rectally administered misoprostol and placebo in a prospective randomized placebo-controlled study. METHODS: One hundred and fifty women with singleton vaginal deliveries were randomized (50 women in each arm) to receive 400-microg misoprostol tablets (crushed and suspended in a microenema) intravaginally, or 400-microg misoprostol tablets rectally, or two placebo lactose tablets rectally. The medication was administered immediately after delivery of the placenta. Women with profuse hemorrhage and delayed placental separation (>30 min) were excluded. Our outcome measures were postpartum blood loss 1 h after administration, and change in hemoglobin and hematocrit values from baseline to postpartum day 1. Analysis of variance and chi-squared tests were used to compare the outcome variables between groups. RESULTS: One hundred and twenty-six women were available for analysis. Baseline characteristics were similar across the groups. The number of excluded subjects, the estimated blood loss, and the drop in hemoglobin and hematocrit values did not differ between the three groups (P > 0.05). CONCLUSIONS: Misoprostol administered vaginally or rectally at a dosage of 400 microg following placental separation was not effective for decreasing postpartum bleeding in women without excessive hemorrhage.     

A survey of emergency department use in patients with cyclic vomiting syndrome

Background

The Bonfils intubating fiberscope has a limited upward tip angle of 40° and requires retromolar entry into the hypopharynx. These factors may make its use less desirable when managing the difficult airway because most anesthesia providers are well versed in midline oral intubation rather than the lateral retromolar approach. The Center for Advanced Technology and Telemedicine at the University of Nebraska Medical Center has developed a novel fiberscope with a more anterior 60° curve to allow for easier midline insertion and intubation. The objective of this work was to evaluate the novel fiberscope, in comparison to the Bonfils intubating fiberscope, in terms of use and function in difficult airway intubation.

Methods

Twenty-two anesthesia providers participated in simulated intubations of a difficult airway mannequin to compare the Bonfils intubating fiberscope with the novel curved Boedeker intubating fiberscope. The intubations were assessed based upon the following variables: recorded Cormack Lehane airway scores, requests for cricoid pressure, time to intubation, number of intubation attempts and success or failure of the procedure.

Results

Participants using the Bonfils fiberscope recorded an average Cormack Lehane (CL) airway score of 1.67 ± 1.02 (median = 1); with the novel fiberscope, the recorded average airway grade improved to 1.18 ± 0.50 (median = 1). The difference in airway scores was not statistically significant (p = 0.34; Fishers Exact Test comparing CL grades 1&2 vs. 3&4). There was, however, a statistically significant difference in intubation success rates between the two devices. With the Bonfils fiberscope, 68% (15/22) of participants were successful in intubation compared to a 100% success rate in intubation with the novel fiberscope (22/22) (p = 0.008). After the intubation trial, the majority of participants (95%) indicated a preference for the novel fiberscope (n = 20).

Conclusions

With this data, we can infer that the novel fiberscope curvature appears to improve or maintain the quality of an intubation attempt (airway score, cricoid pressure requirement, intubation time, number of attempts, placement success). The data indicate that the novel fiberscope offers a superior intubation experience to currently available best practices. The instrument was well received and would be welcomed by most study participants should the device become clinically available in the future.