Advanced interventions in the pre-hospital resuscitation of patients with non-compressible haemorrhage after penetrating injuries.

Early haemorrhage control and minimizing the time to definitive care have long been the cornerstones of therapy for patients exsanguinating from non-compressible haemorrhage (NCH) after penetrating injuries, as only basic treatment could be provided on scene. However, more recently, advanced on-scene treatments such as the transfusion of blood products, resuscitative thoracotomy (RT) and resuscitative endovascular balloon occlusion of the aorta (REBOA) have become available in a small number of pre-hospital critical care teams. Although these advanced techniques are included in the current traumatic cardiac arrest algorithm of the European Resuscitation Council (ERC), published in 2021, clear guidance on the practical application of these techniques in the pre-hospital setting is scarce. This paper provides a scoping review on how these advanced techniques can be incorporated into practice for the resuscitation of patients exsanguinating from NCH after penetrating injuries, based on available literature and the collective experience of several helicopter emergency medical services (HEMS) across Europe who have introduced these advanced resuscitation interventions into routine practice.

Pre-hospital transfusion of red blood cells in civilian trauma patients.

INTRODUCTION: The current management of severely injured patients includes damage control resuscitation strategies that minimise the use of crystalloids and emphasise earlier transfusion of red blood cells (RBC) to prevent coagulopathy. In 2012, London's air ambulance (LAA) became the first UK civilian pre-hospital service to routinely carry RBC to the trauma scene. OBJECTIVE: To investigate the effect of pre-hospital RBC transfusion (phRTx) on overall blood product consumption. METHODS: A retrospective trauma database study compares before implementation with after implementation of phRTx in exsanguinating trauma patients transported directly to one major trauma centre. Pre-hospital deaths were excluded. Univariate and multivariate Poisson regression analyses on data subject to multiple imputation were conducted. RESULTS: We included 137 and 128 patients in the before and after the implementation of phRTx groups, respectively. LAA transfused 304 RBC units (median 2, inter quartile range 1-3). We found a significant reduction in total RBC usage and reduced early use of platelets and fresh-frozen plasma (FFP) after the implementation of phRTx in both univariate (P < 0·001) and multivariate analyses (P < 0·001). No immediate adverse transfusion reactions were identified. CONCLUSION: Pre-hospital trauma transfusion practice is feasible and associated with overall reduced RBC, platelets and FFP consumption.

Pre-hospital emergency anaesthesia in awake hypotensive trauma patients: beneficial or detrimental?

BACKGROUND: The benefits of pre-hospital emergency anaesthesia (PHEA) are controversial. Patients who are hypovolaemic prior to induction of anaesthesia are at risk of severe cardiovascular instability post-induction. This study compared mortality for hypovolaemic trauma patients (without major neurological injury) undergoing PHEA with a patient cohort with similar physiology transported to hospital without PHEA. METHODS: A retrospective database review was performed to identify patients who were hypotensive on scene [systolic blood pressure (SBP) < 90 mmHg], and GCS 13-15. Patient records were reviewed independently by two pre-hospital clinicians to identify the likelihood of hypovolaemia. Primary outcome measure was mortality defined as death before hospital discharge. RESULTS: Two hundred and thirty-six patients were included; 101 patients underwent PHEA. Fifteen PHEA patients died (14.9%) compared with six non-PHEA patients (4.4%), P = 0.01; unadjusted OR for death was 3.73 (1.30-12.21; P = 0.01). This association remained after adjustment for age, injury mechanism, heart rate and hypovolaemia (adjusted odds ratio 3.07 (1.03-9.14) P = 0.04). Fifty-eight PHEA patients (57.4%) were hypovolaemic prior to induction of anaesthesia, 14 died (24%). Of 43 PHEA patients (42.6%) not meeting hypovolaemia criteria, one died (2%); unadjusted OR for mortality was 13.12 (1.84-578.21). After adjustment for age, injury mechanism and initial heart rate, the odds ratio for mortality remained significant at 9.99 (1.69-58.98); P = 0.01. CONCLUSION: Our results suggest an association between PHEA and in-hospital mortality in awake hypotensive trauma patients, which is strengthened when hypotension is due to hypovolaemia. If patients are hypovolaemic and awake on scene it might, where possible, be appropriate to delay induction of anaesthesia until hospital arrival.

Inter-disciplinary cooperation in a physician-staffed emergency medical system.

BACKGROUND: On-scene management of pre-hospital emergencies is often inter-disciplinary, involving ground-emergency medical services (EMS), police- and fire services, and in Norway general practitioners on-call. This can also be supplemented by physician-staffed EMS (P-EMS), utilizing helicopters or rapid response vehicles. We hypothesized that P-EMS cooperates extensively with other emergency services, and therefore the primary aim of this study was to investigate the fraction of inter-disciplinary cooperation between P-EMS and other emergency services. METHODS: Retrospective, observational study of primary pre-hospital missions with patient contact performed at a Norwegian P-EMS base from 01.01.06 to 31.12.15. Descriptive statistics, comparisons using Student`s t-test, and chi-squared test for trend were applied. RESULTS: Inter-disciplinary cooperation occurred in 94.3% of the 8580 missions, of which physician-staffed EMS cooperated with ground EMS in 92.4%, general practitioner 32.9%, police service 11.6% and fire service 11.8%. Trauma constituted 34.4 and cardiac arrest 14.1% of missions. The mean National Advisory Committee for Aeronautics score was 4.21 (95% Confidence Interval 4.18-4.24). There was an overall decrease in cooperation with general practitioners and the police service (P < 0.001). During helicopter missions, we reported a decrease in general practitioner cooperation compared to an increase during rapid response car missions (P < 0.001). In cardiac arrest cases, cooperation with both general practitioners and the fire service increased (P < 0.001). CONCLUSION: Physician-staffed EMS cooperates extensively with other professional emergency services, especially ground-EMS. On-scene cooperation with general practitioners decreased, whereas there was an increased cooperation with the fire service in a "first-responder" role during cardiac arrest missions.

The success of pre-hospital tracheal intubation by different pre-hospital providers: a systematic literature review and meta-analysis.

BACKGROUND: Pre-hospital basic airway interventions can be ineffective at providing adequate oxygenation and ventilation in some severely ill or injured patients, and advanced airway interventions are then required. Controversy exists regarding the level of provider required to perform successful pre-hospital intubation. A previous meta-analysis reported pre-hospital intubation success rates of 0.849 for non-physicians versus 0.991 for physicians. The evidence base on the topic has expanded significantly in the last 10 years. This study systematically reviewed recent literature and presents comprehensive data on intubation success rates. METHODS: A systematic search of MEDLINE and EMBASE was performed using PRISMA methodology to identify articles on pre-hospital tracheal intubation published between 2006 and 2016. Overall success rates were estimated using random effects meta-analysis. The relationship between intubation success rate and provider type was assessed in weighted linear regression analysis. RESULTS: Of the 1838 identified studies, 38 met the study inclusion criteria. Intubation was performed by non-physicians in half of the studies and by physicians in the other half. The crude median (range) reported overall success rate was 0.969 (0.616-1.000). In random effects meta-analysis, the estimated overall intubation success rate was 0.953 (0.938-0.965). The crude median (range) reported intubation success rates for non-physicians were 0.917 (0.616-1.000) and, for physicians, were 0.988 (0.781-1.000) (p = 0.003). DISCUSSION: The reported overall success rate of pre-hospital intubation has improved, yet there is still a significant difference between non-physician and physician providers. The finding that less-experienced personnel perform less well is not unexpected, but since there is considerable evidence that poorly performed intubation carries a significant risk of morbidity and mortality careful consideration should be given to the training and experience required to deliver this intervention safely.

Targeted sequencing of BRCA1 and BRCA2 across a large unselected breast cancer cohort suggests that one-third of mutations are somatic.

BACKGROUND: A mutation found in the BRCA1 or BRCA2 gene of a breast tumor could be either germline or somatically acquired. The prevalence of somatic BRCA1/2 mutations and the ratio between somatic and germline BRCA1/2 mutations in unselected breast cancer patients are currently unclear. PATIENTS AND METHODS: Paired normal and tumor DNA was analyzed for BRCA1/2 mutations by massively parallel sequencing in an unselected cohort of 273 breast cancer patients from south Sweden. RESULTS: Deleterious germline mutations in BRCA1 (n = 10) or BRCA2 (n = 10) were detected in 20 patients (7%). Deleterious somatic mutations in BRCA1 (n = 4) or BRCA2 (n = 5) were detected in 9 patients (3%). Accordingly, about 1 in 9 breast carcinomas (11%) in our cohort harbor a BRCA1/2 mutation. For each gene, the tumor phenotypes were very similar regardless of the mutation being germline or somatically acquired, whereas the tumor phenotypes differed significantly between wild-type and mutated cases. For age at diagnosis, the patients with somatic BRCA1/2 mutations resembled the wild-type patients (median age at diagnosis, germline BRCA1: 41.5 years; germline BRCA2: 49.5 years; somatic BRCA1/2: 65 years; wild-type BRCA1/2: 62.5 years). CONCLUSIONS: In a population without strong germline founder mutations, the likelihood of a BRCA1/2 mutation found in a breast carcinoma being somatic was ∼1/3 and germline 2/3. This may have implications for treatment and genetic counseling.

Scandinavian SSAI clinical practice guideline on pre-hospital airway management.

BACKGROUND: The Scandinavian society of anaesthesiology and intensive care medicine task force on pre-hospital airway management was asked to formulate recommendations following standards for trustworthy clinical practice guidelines. METHODS: The literature was systematically reviewed and the grading of recommendations assessment, development and evaluation (GRADE) system was applied to move from evidence to recommendations. RESULTS: We recommend that all emergency medical service (EMS) providers consider to: apply basic airway manoeuvres and airway adjuncts (good practice recommendation); turn unconscious non-trauma patients into the recovery position when advanced airway management is unavailable (good practice recommendation); turn unconscious trauma patients to the lateral trauma position while maintaining spinal alignment when advanced airway management is unavailable [strong recommendation, low quality of evidence (QoE)]. We suggest that intermediately trained providers use a supraglottic airway device (SAD) or basic airway manoeuvres on patients in cardiac arrest (weak recommendation, low QoE). We recommend that advanced trained providers consider using an SAD in selected indications or as a rescue device after failed endotracheal intubation (ETI) (good practice recommendation). We recommend that ETI should only be performed by advanced trained providers (strong recommendation, low QoE). We suggest that videolaryngoscopy is considered for ETI when direct laryngoscopy fails or is expected to be difficult (weak recommendation, low QoE). We suggest that advanced trained providers apply cricothyroidotomy in 'cannot intubate, cannot ventilate' situations (weak recommendation, low QoE). CONCLUSION: This guideline for pre-hospital airway management includes a combination of techniques applied in a stepwise fashion appropriate to patient clinical status and provider training.

[Prognostic factors of perinatal short-term outcome in severe placental insufficiency using Doppler sonography to assess end-diastolic absent and reverse blood flow in umbilical arteries]. / Prognosefaktoren des perinatalen Kurzzeitergebnisses bei schwerer Plazentainsuffizienz mit dopplersonografisch enddiastolischem Null- und Rückfluss in der Art. umbilicalis.

Significant placental insufficiency, indicated by Doppler ultrasound findings of absent or reverse end-diastolic flow velocities (AREDV), is associated with increased morbidity and mortality. Analysis of blood flow in the ductus venosus should assist in early intrauterine recognition of threatened foetuses. 58 high-risk pregnancies with umbilical AREDV were repeatedly examined (n=364). Doppler findings were correlated with neonatal signs of deterioration (ratio of normoblasts to leukocytes, pH, base excess, Apgar score), as well as short-term morbidity [need for intubation, duration of assisted respiration, evidence of respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), necrotising enterocolitis (NEC), intraventricular haemorrhage (IVH grade III+IV)] against the analysis of the blood flow findings (normal or increased pulsitility, absence or reverse end-diastolic flow) in the umbilical arteries (AU), the middle cerebral arteries (ACM) and ductus venosus (DV) relating these to birth weight and the duration of the pregnancy. The median period of observation was 12.8 days, 48% of the foetuses showed an abnormal ductus venosus flow and 26% an absent venous or reverse end-diastolic flow. The median date of delivery was 30 weeks, with a mean birth weight of 816 g. 93% were live births with 12% dying postnatally. Although the criteria for postnatal morbidity (BPD, NEC, IVH III+IV) and mortality did not correlate with changes in arterial and venous Doppler parameters in our group, there was a significant relationship between the normoblast count, known to be a marker of chronic hypoxia. The Apgar 10 minte score, umbilical arterial pH and base excess were correlated with changes in the DV flow curves. Healthy survival started, irrespective of arterial or venous blood flow criteria, from 27+0 weeks of pregnancy. If born between 27.0 and 30+6 weeks, the infants were more likely to be healthy the less the blood flow had been compromised. A birth weight of 590 g (sensitivity 62.5%; specificity 93.5%) and gestational age of 28+5 weeks (sensitivity 87.5%; specificity 90.3%) were shown to be cut-off points between healthy survival and survival with serious neonatal complications.

Attributes of leadership skill development in high-performance pre-hospital medical teams: results of an international multi-service prospective study.

BACKGROUNDS: Team leadership skills of physicians working in high-performing medical teams are directly related to outcome. It is currently unclear how these skills can best be developed. Therefore, in this multi-national cross-sectional prospective study, we explored the development of these skills in relation to physician-, organization- and training characteristics of Helicopter Emergency Medicine Service (HEMS) physicians from services in Europe, the United States of America and Australia. METHODS: Physicians were asked to complete a survey regarding their HEMS service, training, and background as well as a full Leader Behavior Description Questionnaire (LBDQ). Primary outcomes were the 12 leadership subdomain scores as described in the LBDQ. Secondary outcome measures were the association of LBDQ subdomain scores with specific physician-, organization- or training characteristics and self-reported ways to improve leadership skills in HEMS physicians. RESULTS: In total, 120 HEMS physicians completed the questionnaire. Overall, leadership LBDQ subdomain scores were high (10 out of 12 subdomains exceeded 70% of the maximum score). Whereas physician characteristics such as experience or base-specialty were unrelated to leadership qualities, both organization- and training characteristics were important determinants of leadership skill development. Attention to leadership skills during service induction, ongoing leadership training, having standards in place to ensure (regular) scenario training and holding structured mission debriefs each correlated with multiple LBDQ subdomain scores. CONCLUSIONS: Ongoing training of leadership skills should be stimulated and facilitated by organizations as it contributes to higher levels of proficiency, which may translate into a positive effect on patient outcomes. TRIAL REGISTRATION: Not applicable.

Unusual increase of psittacosis in southern Sweden linked to wild bird exposure, January to April 2013.

Free-living wild birds worldwide act as reservoir for Chlamydia psittaci, but the risk of transmission to humans through contact with wild birds has not been widely documented. From 12 January to April 9 2013, a total of 25 cases of psittacosis were detected in southern Sweden, about a threefold increase compared with the mean of the previous 10 years. A matched case-control study investigating both domestic and wild bird exposure showed that cases were more likely than controls to have cleaned wild bird feeders or been exposed to wild bird droppings in other ways (OR: 10.1; 95% CI: 2.1-47.9). We recommend precautionary measures such as wetting bird feeders before cleaning them, to reduce the risk of transmission of C. psittaci when in contact with bird droppings. Furthermore, C. psittaci should be considered for inclusion in laboratory diagnostic routines when analysing samples from patients with atypical pneumonia, since our findings suggest that psittacosis is underdiagnosed.

[Unexpected respiratory distress in the delivery room--a rare differential diagnosis for the obstetrician and neonatologist]. / Unerwartete Atemnot im Kreißsaal--eine seltene Differenzialdiagnose für Geburtshelfer und Neonatologen.

We present the case of a female infant born prematurely at 34 weeks of gestation. Prenatally a midsized ventricular septal defect was diagnosed. Due to marked respiratory distress intubation was attempted but failed, since the tube could not be placed beyond the glottis. Oxygenation could be improved by nasopharyngeal bag ventilation. The clinical course as well as radiographic imaging was suggestive for a complete tracheal agenesis with broncho-oesophageal fistula which was confirmed at autopsy. Tracheal agenesis (TA) is a rare differential diagnosis of postnatal respiratory distress and the obstetrician or neonatologist will regularly be surprised by this malformation. Partial or complete absence of the trachea without associated malformations will be rarely diagnosed antenatally. In the case of the absence of an oesophageal fistula to the remaining airway a congenital high airway obstruction syndrome (CHAOS) ensues, leading to enlarged hyperechogenic lungs, dilated and fluid-filled trachea and bronchi and an absent tracheal flow during foetal breathing. Aetiology of TA is unknown, therapeutic options are limited thus making TA a usually fatal disorder.

Efficacy of a two-tiered trauma team activation protocol in a Norwegian trauma centre.

BACKGROUND: A registry-based analysis revealed imprecise informal one-tiered trauma team activation (TTA) in a primary trauma centre. A two-tiered TTA protocol was introduced and analysed to examine its impact on triage precision and resource utilization. METHODS: Interhospital transfers and patients admitted by non-healthcare personnel were excluded. Undertriage was defined as the fraction of major trauma victims (New Injury Severity Score over 15) admitted without TTA. Overtriage was the fraction of TTA without major trauma. RESULTS: Of 1812 patients, 768 had major trauma. Overall undertriage was reduced from 28·4 to 19·1 per cent (P < 0·001) after system revision. Overall overtriage increased from 61·5 to 71·6 per cent, whereas the mean number of skilled hours spent per overtriaged patient was reduced from 6·5 to 3·5 (P < 0·001) and the number of skilled hours spent per major trauma victim was reduced from 7·4 to 7·1 (P < 0·001). Increasing age increased risk for undertriage and decreased risk for overtriage. Falls increased risk for undertriage and decreased risk for overtriage, whereas motor vehicle-related accidents showed the opposite effects. Patients triaged to a prehospital response involving an anaesthetist had less chance of both undertriage and overtriage. CONCLUSION: A two-tiered TTA protocol was associated with reduced undertriage and increased overtriage, while trauma team resource consumption was reduced. REGISTRATION NUMBER: NCT00876564 (http://www.clinicaltrials.gov).

[Sonographic abnormalities of the fetal CNS in the second trimester screening--clarifications according to the new maternity directives]. / Sonografische Auffälligkeiten des fetalen ZNS im Zweittrimesterscreening--Abklärung nach neuen Mutterschaftsrichtlinien.

Malformations of the central nervous system are among the most frequent congenital anomalies. At best, a qualified and standardised screening of the foetal brain is possible between the 18th and the 22nd week. The newly decided modification of the maternity directives envisages an extended screening upon request. This extended screening refers to the central nervous system and the representation of the ventricles, the evaluation of the head shape and the cerebellum and the back. The examination of the foetal brain should be carried out in a structured way. Three axial planes, the transventricular, the transthalamic and the transcerebellar planes, suffice to represent and measure all structures which are of importance for the screening. In case of ventricular anomalies, anomalies of the head shape, anomalies of the cerebellum and irregularities of the dorsal skin outlined in the second screening a further diagnostic procedure should be initiated. This diagnostic work-up should include a detailed neurosonography, a diagnostic evaluation of the organs and eventually further examination in the form of a caryotyping, determination of the infectology or a foetal MRI. The present article offers an overview of possible CNS abnormalities which could be recognised during the second screening according to the extended maternity directives and describes which differential diagnostics should be considered. In detail, anomalies of the head size (microcephaly, macrocephaly), of the head size (brachycephaly, dolichocephaly, cavities of the cranium, banana sign, etc.,), ventricular abnormalities, anomalies of the cerebellum (cerebellum hypoplasia, abnormal cerebellum shape) and abnormalities of the intermediate line and the intracerebral space requirements are discussed.

[Acute foeto-foetal transfusion syndrome--case report and review of the literature]. / Akutes fetofetales Transfusionssyndrom--Fallbericht und Literaturübersicht.

The perinatal morbidity and mortality risk in monochorionic twin pregnancies are 3-5-fold increased compared to those of dichorionic twin pregnancies. Partially, this is due to the higher rate of preterm delivery but also to the twin-to-twin transfusion syndrome (TTTS). Caused by unidirectional blood flow via placental anastomoses, the TTTS leads to weight differences of more than 20% between monochorial twins. The blood donor often shows oligohydramnios, whereas the recipient shows polyhydramnios. Lewi et al. demonstrated, in a study with 202 monochorionic twin pregnancies, a 9% rate of severe TTTS. The mortality of this complication is about 90% when untreated. In contrast to the chronic TTTS, little is known about the acute intrapartal one, which is characterised by anaemia and hypovolaemia of the donor and polyglobulia of the recipient without significant weight differences between the two. In most cases, anaemia occurred after normal delivery of the first twin. Still, there are no means or signs for early detection. We describe the case of a 30-year-old primigravida with a monochorionic diamniotic twin pregnancy. During pregnancy, no evidence of TTTS could be detected. At 37 + 1 weeks gestation labour was induced with prostaglandin-containing gel. Both foetuses showed cephalic presentation. The CTG of the first twin showed a conspicuous heart rate. After labour the first twin presented with anaemia and hypovolaemic shock, the APGAR was 2/7/8. The infant's haemoglobin was 13.7 g/dL. After delivery, the second twin with APGAR 10/10/10 showed a haemoglobin of 19.6 g/dL, which is in the upper normal range. Their birth weights differed by merely 10.4%. Acute TTTS is frequently characterised by anaemia and hypovolaemia of the second twin. In our case of a monochorionic twin delivery with acute TTTS the donor was born first. Early diagnosis and neonatal intervention is essential for reducing postnatal morbidity and mortality.

Collagen levels are normalized after decompression of experimentally obstructed colon.

AIM: Our aim was to define the dynamics in collagen concentrations in the large bowel wall following decompression of experimental obstruction. METHOD: Colonic obstruction was created in 28 male rats by the placement of a silicone ring around the distal colon. The ring was removed after 4 days to mimic endoscopical decompression by stent deployment. Colon circumference and collagen concentration were measured proximal to the obstructed segment immediately and at 3 and 10 days after decompression. The corresponding colonic sites of 23 sham-operated and eight nonoperated control animals were subjected to identical analyses. RESULTS: Four days of obstruction resulted in a more than twofold increase in colonic circumference (20 vs 8 mm), with a concomitant 43% reduction (P = 0.001) in collagen concentration in the bowel wall proximal to the obstruction compared with sham animals. Three days after decompression, collagen concentrations remained reduced (P < 0.05), while there was no significant difference after 10 days with either sham-operated or nonoperated controls. Colonic circumference of the obstructed colon remained slightly distended (11 mm) on day 10 and tended to correlate (r(S) = 0.51, P = 0.053) with total matrix metalloproteinase activity. CONCLUSION: The marked reduction in collagen concentration in an experimentally obstructed colon is normalized 10 days after decompression. These findings may have clinical implications for the timing of surgical resection.

[Obstetric management of fetal growth retardation]. / Geburtshilfliches Management bei fetaler Retardierung.

Intrauterine growth restriction (IGUR) can have different etiologies, but placental insufficiency is the clinically most relevant. Fetuses with IUGR have a significantly higher morbidity and mortality than normally grown fetuses of the same gestational age. It is important to distinguish a growth restricted fetus from a normal, small fetus and from a fetus being small because of a disease, e.g., an aneuploidy. This differentiation requires the knowledge of the gestational age and the use of multiple imaging modalities. Serial assessments of fetal growth by ultrasound are necessary to recognize declining growth. Doppler sonography can detect changes in the uteroplacentar and the fetal perfusion. Blood vessels of clinical relevance are the uterine arteries, the umbilical artery, the middle cerebral artery and the ductus venosus. When no fetal anomalies can be detected, fetal growth is parallel to the percentiles and Doppler sonography measurements are normal, IUGR is unlikely. In most IUGR fetuses, a typical sequence of circulatory changes and ultrasound findings can be observed. As there is no evidence-based treatment option for IUGR until now, obstetric management consists in defining the optimal time of delivery. This means weighing the risks of prematurity against the risks of a potentially hostile intrauterine environment.

[Late interruption of pregnancy due to foetal disease: is an inductive method for the generation of ethical principles applicable?]. / Spätabbruch von Schwangerschaften bei fetalen Erkrankungen: Führt ein induktives Verfahren der Normgewinnung zu ethischer Klarheit?

BACKGROUND: The current study investigates if an inductive method for the generation of ethical principles can be applied to the crucial moral question if late interruption of pregnancy due to fetal disease is ethically adequate. METHODS: This method originates from the US American philosopher John Rawls and puts a group of so-called competent moral investigators in the beginning of the decision process. These competent moral investigators should be objective, tolerant and sensitive. Thus, real cases which lead to an intuitive, unanimous and clear decision of the competent moral investigators are analysed for the underlying ethical principles. The ethical principles thus detected are then applied to more complicated cases which could not be assessed clearly. RESULTS: In the current study, the case of foetal trisomy 18 and foetal palate cleft could be clearly judged with a yes and a no, respectively, with regard to an approval of late interruption of pregnancy. The underlying ethical principle leading to these decisions is the utilitaristic principle of minimising harm for mother and fetus. DISCUSSION: We then tried to apply this principle to a case of foetal trisomy 21, however, no clear decision for an approval or a disapproval of the interruption of pregnancy could be found as it was not possible to assess foetal interests.

A beta cell-specific knockout of hormone-sensitive lipase in mice results in hyperglycaemia and disruption of exocytosis.

AIMS/HYPOTHESIS: The enzyme hormone-sensitive lipase (HSL) is produced and is active in pancreatic beta cells. Because lipids are known to play a crucial role in normal control of insulin release and in the deterioration of beta cell function, as observed in type 2 diabetes, actions of HSL in beta cells may be critical. This notion has been addressed in different lines of HSL knockout mice with contradictory results. METHODS: To resolve this, we created a transgenic mouse lacking HSL specifically in beta cells, and characterised this model with regard to glucose metabolism and insulin secretion, using both in vivo and in vitro methods. RESULTS: We found that fasting basal plasma glucose levels were significantly elevated in mice lacking HSL in beta cells. An IVGTT at 12 weeks revealed a blunting of the initial insulin response to glucose with delayed elimination of the sugar. Additionally, arginine-stimulated insulin secretion was markedly diminished in vivo. Investigation of the exocytotic response in single HSL-deficient beta cells showed an impaired response to depolarisation of the plasma membrane. Beta cell mass and islet insulin content were increased, suggesting a compensatory mechanism, by which beta cells lacking HSL strive to maintain normoglycaemia. CONCLUSIONS/INTERPRETATION: Based on these results, we suggest that HSL, which is located in close proximity of the secretory granules, may serve as provider of a lipid-derived signal essential for normal insulin secretion.