Workforce planning and training in Obstetrics and Gynaecology across Europe: A survey of national trainee societies.

OBJECTIVE(S): To describe the infrastructural differences in training in Obstetrics and Gynaecology (ObGyn) across Europe. STUDY DESIGN: Descriptive web-based survey of 31 national ObGyn trainee societies representing the 30 member countries of the European Network of Trainees in Obstetrics and Gynaecology. Answers were verified in a telephone interview and only countries which had completed the telephone interview were included in the final analysis. RESULTS: The final analysis included 28 of 31 societies representing 27 countries (response rate 90%). The median formal duration of training was 5 years (range 4-7). There were mandatory requirements in addition to medical school graduation before specialisation could be started in 20 (71%) countries. The job opportunities after completion of training varied and included academic fellowships (n=21 [75%]), clinical fellowships/junior consultancy (n=21 [75%]), consultancy (n=11 [40%]), and private practice (n=23 [82%)]. Training and working as a specialist abroad was uncommon (≤20% in 21 [78%] and 26 [96%] countries respectively). Exams during ObGyn training were offered in 24 (85%) countries. Unemployment after completion of training was rare (<5% in 26 [93%] countries). Assessment of ObGyn specialists took place in 20 (71%) countries. CONCLUSION(S): The study illustrates that there are organisational variations in ObGyn training in Europe; A) The requirements to obtain a training post vary causing differences in the qualifications of trainees starting training. B) The duration of training varies. And C) newly trained specialists carry varying levels of responsibility. The results suggest that the content, organisation, and outcome of training differ across Europe. Differences due to political, social and cultural reasons are expected. However, further harmonisation of training across Europe still seems desirable in order to improve women's healthcare and facilitate the mobility of ObGyn trainees and specialists across Europe. There are currently several European initiatives, however, national and local measures are essential for training to improve.

P2Y1 and P2Y12 receptors in hypoxia- and adenosine diphosphate-induced pulmonary vasoconstriction in vivo in the pig.

PURPOSE: To investigate the role of P2Y1 and P2Y12 receptors in hypoxia- and adenosine diphosphate (ADP)-induced pulmonary vasoconstriction. METHODS: 19 anaesthetized, mechanically ventilated pigs (31.3 ± 0.7 kg) were evaluated in normoxia and hypoxia, without (n = 6) or with P2Y1 receptor antagonist MRS2500 (n = 7) or P2Y12 receptor antagonist cangrelor (n = 6) treatment. 12 pigs (29.3 ± 0.4 kg) were evaluated before and during ADP infusion, without and with MRS2500 (n = 6) or cangrelor (n = 6) pre-treatment. RESULTS: Hypoxia increased (p < 0.05) mean pulmonary artery pressure (MPAP) by 14.2 ± 1.1 mmHg and pulmonary vascular resistance (PVR) by 2.7 ± 0.4 WU. Without treatment MPAP and PVR remained unaltered (p = ns) for 90 min hypoxia. During hypoxia MRS2500 decreased (p < 0.013) MPAP by 4.3 ± 1.2 mmHg within 15 min. Cangrelor decreased (p < 0.036) MPAP to be 3.3 ± 0.4 and 3.6 ± 0.6 mmHg lower than hypoxia baseline after 10 and 30 min. PVR was, however, unaltered (p = ns) by MRS2500 or cangrelor during hypoxia. ADP increased (p < 0.001) MPAP and PVR to stabilize 11.1 ± 1.3 mmHg and 2.7 ± 0.3 WU higher than baseline. MRS2500 or cangrelor pre-treatment totally abolished the sustained MPAP- and PVR-increases to ADP. CONCLUSIONS: ADP elicits pulmonary vasoconstriction through P2Y1 and P2Y12 receptor activation. ADP is not a mandatory modulator, but may still contribute to pulmonary vascular tone during acute hypoxia. Further investigations into the mechanisms behind ADP-induced pulmonary vasoconstriction and the role of ADP as a modulator of pulmonary vascular tone during hypoxia are warranted.

Adenosine diphosphate reduces infarct size and improves porcine heart function after myocardial infarct.

Acute myocardial infarction continues to be a major cause of morbidity and mortality. Timely reperfusion can substantially improve outcomes and the administration of cardioprotective substances during reperfusion is therefore highly attractive. Adenosine diphosphate (ADP) and uridine-5-triphoshate (UTP) are both released during myocardial ischemia, influencing hemodynamics. Both mediate the release of tissue plasminogen activator (t-PA), which can reduce infarct size (IS). The objective of this study was to investigate whether exogenous ADP and UTP administration during reperfusion could reduce myocardial IS and whether this correlated to t-PA release or improvements in hemodynamic responses. Hemodynamic variables and t-PA were measured in 22 pigs before, during, and after 45 min of left anterior coronary artery occlusion. During reperfusion, the pigs were randomized to 240 min of intracoronary infusion of ADP, UTP, or control (no intervention). Ischemic area compared to the area at risk [IS/AAR] was measured. [IS/AAR] was 52 ± 11% in the control animals. ADP decreased [IS/AAR] by 19% (P < 0.05), while UTP increased [IS/AAR] by 15% (P < 0.05). Cardiac output (CO) increased from 3.4 to 3.5 L/min (P < 0.05) and mean arterial pressure (MAP) decreased from 87 to 73 mmHg in the ADP group (P < 0.05). t-PA concentration increased in the ADP and UTP group from 2.0 ng/mL to 2.5 and 2.4 ng/mL, respectively (P < 0.05) but remained unchanged in the control group. In conclusion, intracoronary ADP infusion during reperfusion reduces IS by ∼20% independently from systemic release of t-PA. ADP-induced reduction in both preload and afterload could account for the beneficial myocardial effect.

Functional sympatholysis during exercise in patients with type 2 diabetes with intact response to acetylcholine.

OBJECTIVE: Sympathetic vasoconstriction is blunted in contracting human skeletal muscles (functional sympatholysis). In young subjects, infusion of adenosine and ATP increases blood flow, and the latter compound also attenuates α-adrenergic vasoconstriction. In patients with type 2 diabetes and age-matched healthy subjects, we tested 1) the sympatholytic capacity during one-legged exercise, 2) the vasodilatory capacity of adenosine and ATP, and 3) the ability to blunt α-adrenergic vasoconstriction during ATP infusion. RESEARCH DESIGN AND METHODS: In 10 control subjects and 10 patients with diabetes and normal endothelial function, determined by leg blood flow (LBF) response to acetylcholine infusion, we measured LBF and venous NA, with and without tyramine-induced sympathetic vasoconstriction, during adenosine-, ATP-, and exercise-induced hyperemia. RESULTS: LBF during acetylcholine did not differ significantly. LBF increased ninefold during exercise and during adenosine- and ATP-induced hyperemia. Infusion of tyramine during exercise did not reduce LBF in either the control or the patient group. During combined ATP and tyramine infusions, LBF decreased by 30% in both groups. Adenosine had no sympatholytic effect. CONCLUSIONS: In patients with type 2 diabetes and normal endothelial function, functional sympatholysis was intact during moderate exercise. The vasodilatory response for adenosine and ATP did not differ between the patients with diabetes and the control subjects; however, the vasodilatory effect of adenosine and ATP and the sympatholytic effect of ATP seem to decline with age.

Effects of nucleotides and nucleosides on coagulation.

Nucleotides, including ADP, ATP and uridine triphosphate (UTP), are discharged profusely in the circulation during many pathological conditions including sepsis. Sepsis can cause hypotension and systemic activation of the coagulation and fibrinolytic systems in humans, which may cause disseminated intravascular coagulation. We investigated whether nucleotide-induced cardiovascular collapse as provoked by systemic infusion of adenosine, ADP, ATP, UTP and nitric oxide affected the haemostatic system as assessed by whole blood thromboelastography (TEG) analysis. Ten pigs received a randomized infusion of adenosine, ADP, ATP, UTP or nitric oxide until mean arterial pressure was reduced to approximately 40% of baseline simulating sepsis-induced hypotension. The effect of the infusions on the haemostatic system was evaluated by TEG, and endothelial release of tissue plasminogen activator and plasminogen activator inhibitor-1 was measured. In contrast to the other infused substrates, ADP caused a reduction in maximum amplitude (71.4 to 64.2; P < 0.05), and reduced the angle, representing the thrombus formation (75.6 to 66.4; P < 0.05), indicating hypocoagulation. Despite increases in t-PA release (2.1 to 2.7 ng/ml; P < 0.05) and reductions in plasminogen activator inhibitor (33.9 +/- 10.9-17.8 +/- 4.4 ng/ml; P < 0.05) no increased fibrinolysis was found when whole blood was evaluated by TEG. Circulating ADP induces hypocoagulation without signs of increased fibrinolysis as evaluated by TEG. The potential clinical significance of these findings should be investigated further because ADP discharged systemically may possibly contribute to the coagulopathy observed in severe sepsis.

Attenuated purinergic receptor function in patients with type 2 diabetes.

OBJECTIVE: Extracellular nucleotides and nucleosides are involved in regulation of skeletal muscle blood flow. Diabetes induces cardiovascular dysregulation, but the extent to which the vasodilatatory capacity of nucleotides and nucleosides is affected in type 2 diabetes is unknown. The present study investigated 1) the vasodilatatory effect of ATP, uridine-triphosphate (UTP), and adenosine (ADO) and 2) the expression and distribution of P2Y(2) and P2X(1) receptors in skeletal muscles of diabetic subjects. RESEARCH DESIGN AND METHODS: In 10 diabetic patients and 10 age-matched control subjects, leg blood flow (LBF) was measured during intrafemoral artery infusion of ATP, UTP, and ADO, eliciting a blood flow equal to knee-extensor exercise at 12 W (approximately 2.6 l/min). RESULTS: The vasodilatatory effect of the purinergic system was 50% lower in the diabetic group as exemplified by an LBF increase of 274 +/- 37 vs. 143 +/- 26 ml/micromol ATP x kg, 494 +/- 80 vs. 234 +/- 39 ml/micromol UTP x kg, and 14.9 +/- 2.7 vs. 7.5 +/- 0.6 ml/micromol ADO x kg in control and diabetic subjects, respectively, thus making the vasodilator potency as follows: UTP control subjects (100) > ATP control subjects (55) > UTP diabetic subjects (47) > ATP diabetic subjects (29) > ADO control subjects (3) > ADO diabetic subjects (1.5). The distribution and mRNA expression of receptors were similar in the two groups. CONCLUSIONS: The vasodilatatory effect of the purinergic system is severely reduced in type 2 diabetic patients. The potency of nucleotides varies with the following rank order: UTP > ATP > ADO. This is not due to alterations in receptor distribution and mRNA expression, but may be due to differences in receptor sensitivity.

ATP-induced vasodilation and purinergic receptors in the human leg: roles of nitric oxide, prostaglandins, and adenosine.

Plasma ATP is thought to contribute to the local regulation of skeletal muscle blood flow. Intravascular ATP infusion can induce profound limb muscle vasodilatation, but the purinergic receptors and downstream signals involved in this response remain unclear. This study investigated: 1) the role of nitric oxide (NO), prostaglandins, and adenosine as mediators of ATP-induced limb vasodilation and 2) the expression and distribution of purinergic P(2) receptors in human skeletal muscle. Systemic and leg hemodynamics were measured before and during 5-7 min of femoral intra-arterial infusion of ATP [0.45-2.45 micromol/min] in 19 healthy male subjects with and without coinfusion of N(G)-monomethyl-l-arginine (l-NMMA; NO formation inhibitor; 12.3 +/- 0.3 (SE) mg/min), indomethacin (INDO; prostaglandin formation blocker; 613 +/- 12 microg/min), and/or theophylline (adenosine receptor blocker; 400 +/- 26 mg). During control conditions, ATP infusion increased leg blood flow (LBF) from baseline conditions by 1.82 +/- 0.14 l/min. When ATP was coinfused with either l-NMMA, INDO, or l-NMMA + INDO combined, the increase in LBF was reduced by 14 +/- 6, 15 +/- 9, and 39 +/- 8%, respectively (all P < 0.05), and was associated with a parallel lowering in leg vascular conductance and cardiac output and a compensatory increase in leg O(2) extraction. Infusion of theophylline did not alter the ATP-induced leg hyperemia or systemic variables. Real-time PCR analysis of the mRNA content from the vastus lateralis muscle of eight subjects showed the highest expression of P(2Y2) receptors of the 10 investigated P(2) receptor subtypes. Immunohistochemistry showed that P(2Y2) receptors were located in the endothelium of microvessels and smooth muscle cells, whereas P(2X1) receptors were located in the endothelium and the sacrolemma. Collectively, these results indicate that NO and prostaglandins, but not adenosine, play a role in ATP-induced vasodilation in human skeletal muscle. The expression and localization of the nucleotide selective P(2Y2) and P(2X1) receptors suggest that these receptors may mediate ATP-induced vasodilation in skeletal muscle.