Pharmacokinetics of Prophylactic Cefazolin in Parturients Undergoing Cesarean Delivery

The objectives of this work were (i) to characterize the pharmacokinetics of cefazolin in pregnant women undergoing elective cesarean delivery and in their neonates; (ii) to assess cefazolin transplacental transmission; (iii) to evaluate the dosing and timing of preoperative, prophylactic administration of cefazolin to pregnant women; and (iv) to investigate the impact of maternal dosing on therapeutic duration and exposure in newborns. Twenty women received 1 g of cefazolin preoperatively. Plasma concentrations of total cefazolin were analyzed from maternal blood samples taken before, during, and after delivery; umbilical cord blood samples obtained at delivery; and neonatal blood samples collected 24 h after birth. The distribution volume of cefazolin was 9.44 liters/h. The values for pre- and postdelivery clearance were 7.18 and 4.12 liters/h, respectively. Computer simulations revealed that the probability of maintaining free cefazolin concentrations in plasma above 8 mg/liter during scheduled caesarean surgery was <50% in the cord blood when cefazolin was administered in doses of <2 g or when it was administered <1 h before delivery. Therapeutic concentrations of cefazolin persisted in neonates >5 h after birth. Cefazolin clearance increases during pregnancy, and larger doses are recommended for surgical prophylaxis in pregnant women to obtain the same antibacterial effect as in nonpregnant patients. Cefazolin has a longer half-life in neonates than in adults. Maternal administration of up to 2 g of cefazolin is effective and produces exposure within clinically approved limits in neonates.     

Ultrasound imaging of the anal sphincter complex: a review

Endoanal ultrasound is now regarded as the gold standard for evaluating anal sphincter pathology in the investigation of anal incontinence. The advent of three-dimensional ultrasound has further improved our understanding of the two-dimensional technique. Endoanal ultrasound requires specialised equipment and its relative invasiveness has prompted clinicians to explore alternative imaging techniques. Transvaginal and transperineal ultrasound have been recently evaluated as alternative imaging modalities. However, the need for technique standardisation, validation and reporting is of paramount importance. We conducted a MEDLINE search (1950 to February 2010) and critically reviewed studies using the three imaging techniques in evaluating anal sphincter integrity.     

A dynamic test to investigate potential tissue plasminogen activator activity. Comparison of deamino-8-D-argininevasopressin with venous occlusion in normal subjects and patients

Fibrinolysis dependent on the release of tissue plasminogen activator (t-PA) can only be explored after stimulation eliciting the release of t-PA from endothelial cells. The choice of the stimulus and test assay is of utmost importance in discriminating patients at risk for persistent thrombosis and in identifying acquired or genetic abnormalities of t-PA synthesis or release from endothelial cells in pathologic conditions. The present study was designed to compare the efficacy and reproducibility of the fibrinolytic response to desmopressin acetate (deamino-8-D-argininevasopressin) (DDAVP) by use of various routes of administration with the response to the venous occlusion test. Nine healthy male volunteers were randomly administered intravenous desmopressin acetate, intranasal drops and intranasal spray. The results from tests of euglobulin lysis time, t-PA activity, t-PA antigen levels, and t-PA fast-acting inhibitor (plasminogen activator inhibitor [PAI]) level were compared with those obtained after venous occlusion. The only test that elicited the release of free t-PA activity in the circulation in all volunteers was the intravenous administration of 0.4 microgram/kg desmopressin acetate, and the most reliable test assay was t-PA activity measured in the euglobulin fraction of plasma. Intravenous desmopressin acetate induced the release of large amounts of t-PA in most cases and caused a significant fall in PAI. Other routes of administration of desmopressin acetate, along with venous occlusion, identified many nonresponders who proved to be false negative. The relevance of these data was demonstrated in a study in nine patients with thromboembolic phenomenon or related disorders.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of low concentrations versus high concentrations of local anesthetics for labour analgesia on obstetric and anesthetic outcomes: a meta-analysis

Introduction

The influence that different concentrations of labour epidural local anesthetic have on assisted vaginal delivery (AVD) and many obstetric outcomes and side effects is uncertain. The purpose of this meta-analysis was to determine whether local anesthetics utilized at low concentrations (LCs) during labour are associated with a decreased incidence of AVD when compared with high concentrations (HCs).

Methods

We searched PubMed, Ovid EMBASE, Ovid MEDLINE, CINAHL, Scopus, clinicaltrials.gov, and Cochrane databases for randomized controlled trials of labouring patients that compared LCs (defined as ≤ 0.1% epidural bupivacaine or ≤ 0.17% ropivacaine) of epidural local anesthetic with HCs for maintenance of analgesia. The primary outcome was AVD and secondary outcomes included Cesarean delivery, duration of labour, analgesia, side effects (nausea and vomiting, motor block, hypotension, pruritus, and urinary retention), and neonatal outcomes. The odds ratios (OR) or weighted mean differences (WMD) and 95% confidence intervals (CI) were calculated using random effects modelling. An OR < 1 or a WMD < 0 favoured LCs.

Results

Eleven studies met our criteria (eight bupivacaine and three ropivacaine studies), providing 1,145 patients in the LCs group and 852 patients in the HCs group for analysis of the primary outcome. Low concentrations were associated with a reduction in the incidence of AVD (OR = 0.70; 95% CI 0.56 to 0.86; P < 0.001). There was no difference in the incidence of Cesarean delivery (OR 1.05; 95% CI 0.82 to 1.33; P = 0.7). The LCs group had less motor block (OR 3.9; 95% CI 1.59 to 9.55; P = 0.003), greater ambulation (OR 2.8; 95% CI 1.1 to 7.14; P = 0.03), less urinary retention (OR 0.42; 95% CI 0.23 to 0.73; P = 0.002), and a shorter second stage of labour (WMD ?14.03; 95% CI ?27.52 to ?0.55; P = 0.04) compared with the HCs group. There were no differences between groups in pain scores, maternal nausea and vomiting, hypotension, fetal heart rate abnormalities, five-minute Apgar scores, and need for neonatal resuscitation. One-minute Apgar scores < 7 favoured the HCs group (OR 1.53; 95% CI 1.07 to 2.21; P = 0.02), and there was more pruritus in the LCs group (OR 3.36; 95% CI 1.00 to 11.31; P = 0.05).

Conclusion

When compared with HCs of local anesthetics, the use of LCs for labour epidural analgesia reduces the incidence of AVD. This may be due to a reduction in the amount of local anesthetic used and the subsequent decrease in motor blockade. We therefore recommend the use of LCs of local anesthetics for epidural analgesia to optimize obstetric outcome.     

Podophyllum hexandrum Offers Radioprotection by Modulating Free Radical Flux: Role of Aryl-Tetralin Lignans

We have evaluated the effect of variation in aryl-tetralin lignans on the radioprotective properties of Podophyllum hexandrum. Two fractionated fractions of P. hexandrum [methanolic (S1) and chloroform fractions (S2)], with varying aryl-tetralin lignan content were utilized for the present study. The peroxyl ion scavenging potentials of S1 and S2 were found to be comparable [i.e. 45.88% (S1) and 41% (S2)] after a 48 h interval in a time-dependent study, whereas in a 2 h study, S2 exhibited significant (P < 0.05) antioxidant activity in different metal ion + flux states. In the aqueous phase, S2 exhibited non-site-specific reactive oxygen species scavenging activity, i.e. 73.12% inhibition at 500 mug ml(-1). S1 exhibited 58.40 +/- 0.8% inhibition (at 0.025 mug ml(-1)) of the formation of reactive nitrite radicals, comparable to S2 (52.45 +/- 0.825%), and also showed 45.01% site-specific activity (1000 mug ml(-1)), along with significant (P < 0.05) electron donation potential (50-2000 mug ml(-1)) compared to S2. Such activities of S1 could be attributed to the significantly (P < 0.05) higher levels of podophyllotoxin beta-d-glucopyranoside (16.5 times) and demethyl podophyllotoxin glucoside (2.9 times) compared with S2. Together, these findings clearly prove that aryl-tetralin lignan content influences the radiation protective potential of the Podophyllum fractions to a great extent.     

Role of the nurse in patient education and follow-up of people receiving oral chemotherapy treatment: an International survey

PURPOSE: The aim of this study was to explore the nursing role in education and follow-up of patients who were taking oral chemotherapy (CT) and to identify the worldwide gap in patient education about oral CT. MATERIALS AND METHODS: Multinational Association of Supportive Care in Cancer members were invited to participate in a survey on oral CT. Nurse coordinators collected data via a 16-item questionnaire. Respondents totaled 1115 oncology nurses from 15 countries. RESULTS: Findings showed that about half of subjects work in outpatient/ambulatory clinics and had given at least two or more oral CT drugs. Although 52% had some type of guidelines/protocols, 47% reported not having received any education about oral CT drugs. While 64% report being involved in patient education, 58% of subjects indicated lack of patient education materials that are specific for oral CT agents. Only 27% stated that they gave all necessary information such as when and how to take the drugs, drug safety and storage, side effects, and symptom management. Reasons for not being involved in oral CT education and follow-up included beliefs that the physician plans the oral CT and gives patients necessary instructions (34%), that nurses only see patients who receive intravenous chemotherapy (16%), that nurses have lack of knowledge about oral agents (15%), and belief that physicians are responsible for patient follow-up. The nurses suggested better education and follow-up of patients to include the written patient education materials (33%) and professional education for nurses (30%). CONCLUSIONS: Findings revealed the need for professional education for nurses to ensure comprehensive, consistent patient education and development of written materials for patients receiving oral CT treatment.     

Plasma homocysteine levels in obese and non-obese subjects with or without hypertension; its relationship with oxidative stress and copper

OBJECTIVES: The relationship between plasma total Homocysteine (tHcy) and oxidative stress and plasma levels of lipids, insulin and copper levels were investigated in obese and nonobese hypertensives. DESIGN AND METHODS: Plasma tHcy levels were determined by an enzyme immunoassay method. Plasma lipid peroxidation levels were measured as thiobarbituric acid reactive substances (TBARS) by spectrophotometric methods. Plasma levels of copper and insulin were measured by atomic absorption spectrophotometer and electrochemiluminescence method, respectively. RESULTS: Plasma tHcy, copper and insulin levels did not differ in nonobese hypertensives compared to nonobese normotensives. Plasma TBARS levels were significantly increased in nonobese hypertensives when compared to nonobese normotensives (p < 0.001). Plasma tHcy, TBARS, copper and fasting insulin levels were significantly higher in obese normotensives and hypertensives than in nonobese normotensives and hypertensives, respectively (for each comparison; p < 0.001). There was a significant difference in plasma tHcy, TBARS and copper levels between obese subjects with or without hypertension (for each comparison p < 0.01). The univariate analyses demonstrated a significant positive correlation between tHcy and TBARS (coefficient +/- SE, 0.411 +/- 0.115, p < 0.01) and copper (coefficient +/- SE, 0.425 +/- 0.135, p < 0.01) in obese subjects. In a multivariate regression analysis in obese subjects tHcy was positively correlated with TBARS (coefficient +/- SE, 0.480 +/- 0.155, p < 0.01) and copper (coefficient +/- SE, 0.486 +/- 0.140, p < 0.01). CONCLUSIONS: We hypothesize that in the presence of other traditional risk factors, Hcy may have a permissive role in the endothelium damage even within the normal range and this role may be related to free radical generating systems. Therefore, modest elevation of plasma Hcy may causally be involved in the pathogenesis of atherosclerosis and/or cardiovascular disease.