Are routine preoperative liver function tests in patients with uncomplicated symptomatic gallstone disease necessary?

Background: The aim of this study was to evaluate the value of preoperative liver function tests (LFTs) in patients with uncomplicated gallstone disease and scheduled for laparoscopic cholecystectomy.

Methods: All 1112 patients who underwent a laparoscopic cholecystectomy for symptomatic gallstone disease during a 6-year cohort were retrospectively reviewed. Only patients who presented with uncomplicated disease were selected. Preoperative LFTs, pre-, and postoperative endoscopic retrograde cholangio pancreaticographies (ERCPs) and postoperative complications were collected.

Results: A total of 697 patients were included. There were 629 (90.2%) patients with (group I) and 68 (9.8%) patients without (group II) preoperative LFTs. The incidence of ERCPs, ERCPs positive for bile duct stones, and postoperative complications were not significantly different between groups. Second, Group I patients were divided into four groups: 360 patients with normal LFTs (I-A1), 269 patients with at least one LFT?>?normal value (I-A2), 531 patients with all LFTs <2× normal (I-B1), and 98 patients with at least one LFT >2× normal (I-B2). More ERCPs were performed in group I-A2 (10%) than in group I-A1 (2.2%) and more in group I-B2 (18.4%) than I-B1 (3.2%), as a consequence of significantly more ERCPs performed preoperatively. No differences were detected between groups regarding ERCPs positive for bile duct stones or postoperative complications.

Conclusions: Preoperative LFTs do not influence the occurrence of postoperative complications nor the total rate of ERCPs in patients undergoing cholecystectomy for uncomplicated gallstone disease. Preoperative determination of LFTs seems to cause a slight shift from post- to preoperative ERCPs without further clinical consequences.     

Connexin channels provide a target to manipulate brain endothelial calcium dynamics and blood�Cbrain barrier permeability

The cytoplasmic Ca²⁺ concentration ([Ca²⁺]_i) is an important factor determining the functional state of blood–brain barrier (BBB) endothelial cells but little is known on the effect of dynamic [Ca²⁺]_i changes on BBB function. We applied different agonists that trigger [Ca²⁺]_i oscillations and determined the involvement of connexin channels and subsequent effects on endothelial permeability in immortalized and primary brain endothelial cells. The inflammatory peptide bradykinin (BK) triggered [Ca²⁺]_i oscillations and increased endothelial permeability. The latter was prevented by buffering [Ca²⁺]_i with BAPTA, indicating that [Ca²⁺]_i oscillations are crucial in the permeability changes. Bradykinin-triggered [Ca²⁺]_i oscillations were inhibited by interfering with connexin channels, making use of carbenoxolone, Gap27, a peptide blocker of connexin channels, and Cx37/43 knockdown. Gap27 inhibition of the oscillations was rapid (within minutes) and work with connexin hemichannel-permeable dyes indicated hemichannel opening and purinergic signaling in response to stimulation with BK. Moreover, Gap27 inhibited the BK-triggered endothelial permeability increase in in vitro and in vivo experiments. By contrast, [Ca²⁺]_i oscillations provoked by exposure to adenosine 5′ triphosphate (ATP) were not affected by carbenoxolone or Gap27 and ATP did not disturb endothelial permeability. We conclude that interfering with endothelial connexin hemichannels is a novel approach to limiting BBB-permeability alterations.     

Sensitivity to activated protein C during the menstrual cycle in women with and without factor VLeiden

Introduction

Activated protein C (APC) resistance is associated with an increased risk of venous thrombosis. High levels of estradiol and progesterone, e.g. during ovarian stimulation and pregnancy, as well as exogenously administered estrogens and progestagens during oral contraceptive use, induce an acquired form of APC resistance. Several coagulation factors display a cyclic pattern during the menstrual cycle due to the fluctuation of estradiol and progesterone. The aim of the study was to evaluate whether varying levels of estradiol and progesterone during the menstrual cycle are associated with differences in sensitivity to APC.

Materials and methods

Normalized APC sensitivity ratios (nAPCsr) were determined with the thrombin generation-based APC-resistance test at six different time points during the menstrual cycle in thirteen wildtype women and six women with factor V_Leiden.

Results

Mean nAPCsr varied slightly during the menstrual cycle. Women without factor V_Leiden were more likely to have lower nAPCsr at the beginning of the cycle than later on in the cycle (1.34 versus 1.54 and 1.58, Friedman ranking test p = 0.009).

Conclusions

The sensitivity to APC differs between the different phases of the menstrual cycle. This cyclic variability could be useful in improving studies on APC resistance in women.     

Nonagenarian Siblings and Their Offspring Display Lower Risk of Mortality and Morbidity than Sporadic Nonagenarians: The Leiden Longevity Study

OBJECTIVES: To compare the risk of mortality of nonagenarian siblings with that of sporadic nonagenarians (not selected on having a nonagenarian sibling) and to compare the prevalence of morbidity in their offspring with that of the offsprings' partners.
DESIGN: Longitudinal (mortality risk) and cross-sectional (disease prevalence).
SETTING: Nationwide sample.
PARTICIPANTS: The Leiden Longevity Study consists of 991 nonagenarian siblings derived from 420 Caucasian families, 1,365 of their offspring, and 621 of the offsprings' partners. In the Leiden 85-plus Study, 599 subjects aged 85 were included, of whom 275 attained the age of 90 (sporadic nonagenarians).
MEASUREMENTS: All nonagenarian siblings and sporadic nonagenarians were followed for mortality (with a mean±standard deviation follow-up time of 2.7±1.4 years and 3.0±1.5 years, respectively). Information on medical history and medication use was collected for offspring and their partners.
RESULTS: Nonagenarian siblings had a 41% lower risk of mortality ( P <.001) than sporadic nonagenarians. The offspring of nonagenarian siblings had a lower prevalence of myocardial infarction (2.4% vs 4.1%, P =.03), hypertension (23.0% vs 27.5%, P =.01), diabetes mellitus (4.4% vs 7.6%, P =.004), and use of cardiovascular medication (23.0% vs 28.9%, P =.003) than their partners.
CONCLUSION: The lower mortality rate of nonagenarian siblings and lower prevalence of morbidity in their middle-aged offspring reinforce the notion that resilience against disease and death have similar underlying biology that is determined by genetic or familial factors.     

Service quality in hospital wards with different nursing organization: nurses' ratings

Title. Service quality in hospital wards with different nursing organization: nurses’ ratings. Aim. This paper is a report of a study to assess: (1) the relations between nursing organization models in hospital wards and nurses’ perception of the quality of patient care and dimensions of the practice environment, and (2) if these relations were modified by variations in local conditions at the ward level. Background. Previous literature is inconclusive concerning what model of nursing organization maximizes the quality of nursing services. Method. A cross‐sectional survey was carried out in a representative sample of Norwegian hospital wards in 2005. Intra‐ward organization models were classified as: (1) Team leader (n = 30), characterized by extensive responsibilities for team leaders, (2) Primary nurse (n = 18), with extensive responsibilities for named nurses, and (3) Hybrid (n = 37), (1) and (2) combined. We prepared multilevel regression models using scales describing quality of patient care, learning climate, job satisfaction, and relationships with physicians as dependent variables. As independent variables, we used variables representing local ward conditions. Results. Eighty‐seven wards and 1137 nurses (55% response rate) provided complete data. The ward level proportion of variance ranged from 0·10 (job satisfaction) to 0·22 (relationships with physicians). The univariate effect of organization models on quality ratings was not statistically significant. Introducing local ward conditions led to a statistically significant effect of primary nurse organization on relationships with physicians, and to a substantial proportional reduction in ward level variance, ranging from 32% (quality of patient care) to 24% (learning climate). Conclusion. Caution is needed about using service quality arguments when considering the possible benefits and drawbacks of different organizational models.     

Validity and reliability of instruments to assess potential mediators of children's physical activity: A systematic review

This paper aimed to (1) identify potential mediators reported in children's physical activity interventions; and (2) review the psychometric properties of measures of potential mediators included in such interventions. A systematic search of the literature was conducted and studies that reported potential mediators and/or the psychometric properties of measures of potential mediators were retrieved and reviewed. The studies were reviewed for the following psychometric properties: face/logical, construct, and criterion validity; and test–retest and internal consistency (factor analysis and Cronbach's α) reliability. Twenty-one potential mediators were identified from 24 published children's physical activity intervention studies; 17 individual, three social, and one physical environmental. Overall, there was considerable variation in the reporting of the psychometric properties of these measures. Reliability properties (specifically Cronbach's α) were more commonly reported than validity properties; however, for many potential mediators, the quality of these measures was low. Future studies should examine the psychometric properties of measures of potential mediators to ensure appropriate, valid and reliable instruments are used. This will assist in the ability to accurately determine the efficacy of physical activity interventions among children.     

Targeting of doxorubicin to the urinary bladder of the rat shows increased cytotoxicity in the bladder urine combined with an absence of renal toxicity

Targeting of anti-tumor drugs to the urinary bladder for the treatment of bladder carcinoma may be useful, since these agents generally have a low degree of urinary excretion and are highly toxic elsewhere in the body. The anti-tumor drug doxorubicin was coupled to the low-molecular weight protein lysozyme via the acid-sensitive cis-aconityl linker. All free amino groups of the lysozyme were used for drug attachment to achieve intact excretion of the doxorubicin-aconityl-lysozyme conjugate into the bladder. In the bladder, the cytotoxic drug should be regenerated through acidification of the urine. First, the doxorubicin-aconityl-lysozyme conjugate was tested in rats for its target specificity and general toxicity. Wistar rats were injected intravenously with 2 mg/kg free doxorubicin or 10 mg/kg lysozyme-conjugated doxorubicin. Total urinary excretion of doxorubicin was about 10 times higher if the drug was coupled to lysozyme (39 +/- 3% versus 4.4 +/- 0.4%). Free doxorubicin had no detectable toxic effects on heart, liver and lung but caused severe renal damage (proteinuria, N-acetylglucosaminidase excretion and glomerulosclerosis). None of the rats injected with doxorubicin-lysozyme conjugate showed such renal toxicity. Second, we tested whether doxorubicin could be released from the conjugate in the bladder through acidification of the urine and if the released doxorubicin could still exert a cytotoxic effect. Doxorubicin-aconityl-lysozyme (2 mg/kg conjugated doxorubicin, i.v.) was administered in rats with acidified urine (pH 6.1 +/- 0.1) and in rats with a high urinary pH (8.2 +/- 0.4). Ten times more doxorubicin was released from the conjugate in the group with acidified urine (15 +/- 7% versus 1.7 +/- 0.1%). In agreement with this, cytotoxicity was also higher in the low pH group (IC50 of 255 +/- 47 nM versus 684 +/- 84 nM doxorubicin). In conclusion, a specific delivery of doxorubicin to the urinary bladder combined with a reduced toxicity of doxorubicin in the kidneys can be achieved by coupling this anti-tumor drug to the low-molecular weight protein lysozyme via an acid-labile linker. A release of cytotoxic doxorubicin in the urinary bladder can be achieved by acidification of the urine. This technology, after further optimization, may provide an interesting tool for the treatment of bladder carcinoma.