The Tyr113His polymorphism in exon 3 of the microsomal epoxide hydrolase gene is a risk factor for perinatal mortality

BACKGROUND: A genetic predisposition to impaired detoxification of oxidative or chemical stress could play a role in the etiology of perinatal mortality. In this pilot study we investigated the risk of perinatal mortality in relation to genetic polymorphism in microsomal epoxide hydrolase (EPHX) and glutathione S-transferase P1 (GSTP1) in women who experienced perinatal mortality caused by placental pathology, congenital disorders and complications of premature delivery and their male partners. METHODS: Genomic DNA of couples (72 females and 46 males) with a history of perinatal mortality and control couples (71 females and 66 males) with no complications in their obstetric history were analyzed for the presence of the polymorphisms in exon 3 of EPHX (Tyr113His) and GSTP1 (Ile105Val). RESULTS: A similar distribution of the GSTP1 polymorphism was found in all subjects investigated. In women who experienced perinatal mortality, we demonstrated a higher prevalence of the EPHX His113/His113 genotype, which could result in a lower enzyme activity, compared with controls (25% vs. 9%; chi2 = 5.7 and p < 0.02), with an odds ratio (95% confidence interval) of 3.5 (1.1-12.7). CONCLUSION: Our results suggest that the maternal Tyr113His polymorphism in EPHX may be a risk factor for perinatal mortality. However, more research is needed to determine the implication of this finding.     

Effect of fluid loading with saline or colloids on pulmonary permeability, oedema and lung injury score after cardiac and major vascular surgery

Background. The optimal type of fluid for treating hypovolaemiawithout evoking pulmonary oedema is still unclear, particularlyin the presence of pulmonary vascular injury, as may occur aftercardiac and major vascular surgery. Methods. In a single-centre, prospective, single-blinded clinicaltrial 67 mechanically ventilated patients were randomly assignedto receive saline, gelatin 4%, HES 6% or albumin 5%, accordingto a 90 min fluid loading protocol with target central venouspressure of 13 and pulmonary capillary wedge pressure of 15mm Hg, within 3 h after cardiac or major vascular surgery. Beforeand after the protocol, we recorded haemodynamics and ventilatoryvariables and took chest radiographs. The pulmonary vascularinjury was evaluated using the ⁶⁷Ga-transferrin pulmonary leakindex (PLI) and extravascular lung water (EVLW). Plasma colloidosmotic pressure (COP) was determined and the lung injury score(LIS) was calculated. Results. More saline was infused than colloid solutions (P<0.005).The COP increased in the colloid groups and decreased in patientsreceiving saline. Cardiac output increased more in the colloidgroups. At baseline, PLI and EVLW were above normal in 60 and30% of the patients, with no changes after fluid loading, exceptfor a greater PLI decrease in HES than in gelatin-loaded patients.The oxygenation ratio improved in all groups. In the colloidgroups, the LIS increased, because of a decrease in total respiratorycompliance, probably associated with an increase in intrathoracicplasma volume. Conclusions. Provided that fluid overloading is prevented, thetype of fluid used for volume loading does not affect pulmonarypermeability and oedema, in patients with acute lung injuryafter cardiac or major vascular surgery, except for HES thatmay ameliorate increased permeability. During fluid loading,changes in LIS (and respiratory compliance) do not representchanges in pulmonary permeability or oedema.      

Gilbert's syndrome is not associated with HELLP syndrome

The HELLP syndrome has been associated with postpartum unconjugated hyperbilirubinaemia. Several types of disorders cause unconjugated hyperbilirubinaemia, Gilbert's syndrome being the most common. In Caucasians a genetic defect in the TATA box of the promotor region of the gene encoding for bilirubin UDP-glucuronyltransferase is tightly associated with Gilbert's syndrome. This defect was assessed by polymerase chain reaction in 237 women with the HELLP syndrome in their obstetric history and 236 controls. Fifteen percent of the cases and 10% of the controls had a homozygous genetic defect (  χ²= 2.9; P = 0.23  ). No evidence was found that Gilbert's syndrome is associated with the HELLP syndrome.     

What is the Accuracy of Nuclear Imaging in the Assessment of Periprosthetic Knee Infection? A Meta-analysis

Clinical Orthopaedics and Related Research® - In the assessment of possible periprosthetic knee infection, various imaging modalities are used without consensus regarding the most accurate...     

Opinions of the Dutch public on palliative sedation: a mixed-methods approach

Background

Palliative sedation is defined as deliberately lowering a patient’s consciousness, to relieve intolerable suffering from refractory symptoms at the end of life. Palliative sedation is considered a last resort intervention in end-of-life care that should not be confused with euthanasia.

Aim

To inform healthcare professionals about attitudes of the general public regarding palliative sedation.

Design and setting

A cross-sectional survey among members of the Dutch general public followed by qualitative interviews.

Method

One thousand nine hundred and sixty members of the general public completed the questionnaire, which included a vignette describing palliative sedation (response rate 78%); 16 participants were interviewed.

Results

In total, 22% of the responders indicated knowing the term ‘palliative sedation’. Qualitative data showed a variety of interpretations of the term. Eighty-one per cent of the responders agreed with the provision of sedatives as described in a vignette of a patient with untreatable pain and a life expectancy of <1 week who received sedatives to alleviate his suffering. This percentage was somewhat lower for a patient with a life expectancy of <1 month (74%, P = 0.007) and comparable in the case where the physician gave sedatives with the aim of ending the patient’s life (79%, P = 0.54).

Conclusion

Most of the general public accept the use of palliative sedation at the end of life, regardless of a potential life-shortening effect. However, confusion exists about what palliative sedation represents. This should be taken into account by healthcare professionals when communicating with patients and their relatives on end-of-life care options.     

Comparison between quantitative cardiac magnetic resonance perfusion imaging and [15O]H2O positron emission tomography

European Journal of Nuclear Medicine and Molecular Imaging - To compare cardiac magnetic resonance imaging (CMR) with [15O]H2O positron emission tomography (PET) for quantification of absolute...     

Microcomputed tomographic analysis of human condyles in unilateral condylar hyperplasia: increased cortical porosity and trabecular bone volume fraction with reduced mineralisation

Unilateral condylar hyperplasia or hyperactivity is a disorder of growth that affects the mandible, and our aim was to visualise the 3-dimensional bony microstructure of resected mandibular condyles of affected patients. We prospectively studied 17 patients with a clinical presentation of progressive mandibular asymmetry and an abnormal single-photon emission computed tomographic (SPECT) scan. All patients were treated by condylectomy to arrest progression. The resected condyles were scanned with micro-CT (18 μm resolution). Rectangular volumes of interest were selected in 4 quadrants (lateromedial and superoinferior) of the trabecular bone of each condyle. Variables of bone architecture (volume fraction, trabecular number, thickness, and separation, degree of mineralisation, and degree of structural anisotrophy) were calculated with routine morphometric software. Eight of the 17 resected condyles showed clear destruction of the subchondral layer of cortical bone. There was a significant superoinferior gradient for all trabecular variables. Mean (SD) bone volume fraction (25.1 (6) %), trabecular number (1.69 (0.26) mm^-1), trabecular thickness (0.17 (0.03) mm), and degree of mineralisation (695.39 (39.83) mg HA/cm³) were higher in the superior region. Trabecular separation (0.6 (0.16) mm) and structural anisotropy (1.84 (0.28)) were higher in the inferior region. The micro-CT analysis showed increased cortical porosity in many of the condyles studied. It also showed a higher bone volume fraction, greater trabecular thickness and trabecular separation, greater trabecular number, and less mineralisation in the condyles of the 17 patients compared with the known architecture of unaffected mandibular condyles.