Improving the training of the future gynaecologist: development of a European curriculum in Obstetrics and Gynaecology (EBCOG-PACT).

The European Board & College of Obstetrics and Gynaecology has initiated improvement of the European standards of training in Obstetrics and Gynaecology through the project called 'EBCOG-PACT'. In this project, a pan-European curriculum for postgraduate training in Obstetrics and Gynaecology has been developed. The curriculum is societally responsive, and based on the latest medical educational methodology. It consists of the description of outcomes of training for the common Core Curriculum and Electives, the General competencies and soft skills to be trained, and strategies for training of obstetrical skills, gynaecological skills, ultrasound skills and bio-psychosocial and communicative skills. Also, the curriculum provides strategies for assessment through entrustment, a model for portfolio as well as strategies for faculty development and quality management of training. The implementation of the European curriculum in Obstetrics and Gynaecology will provide opportunities for national scientific and professional societies and ministries of health or education to consider modernisation of national or local OBGYN training programs.

The effect of fibroblast growth factor 15 deficiency on the development of high fat diet induced non-alcoholic steatohepatitis.

Non-alcoholic steatohepatitis (NASH) is a form of non-alcoholic fatty liver disease (NAFLD) characterized by steatosis, inflammation, and fibrosis often associated with metabolic syndrome. Fibroblast growth factor 15 (FGF15), an endocrine factor mainly produced in the distal part of small intestine, has emerged to be a critical factor in regulating bile acid homeostasis, energy metabolism, and liver regeneration. We hypothesized that FGF15 alters the development of each of the listed features of NASH. To test this hypothesis, four-week old male Fgf15-/- and their corresponding wild-type (WT) mice were fed either a high fat diet (HFD) or a control chow diet for six months. The results confirmed that HFD feeding for six months in WT mice recapitulated human NASH phenotype, including macrovesicular steatosis, inflammation, and fibrosis. Whereas FGF15 deficiency had no effect on the severity of liver steatosis or inflammation, it was associated with decreased liver fibrosis. Furthermore, FGF15 deficiency resulted in abnormal bile acid homeostasis, increased insulin resistance, increased HFD-induced serum triglycerides, decreased inductions of hepatic cholesterol content by HFD, and altered gene expression of lipid metabolic enzymes. These data suggest that FGF15 improves lipid homeostasis and reduces bile acid synthesis, but promotes fibrosis during the development of NASH.

CES1 genetic variation affects the activation of angiotensin-converting enzyme inhibitors.

The aim of the study was to determine the effect of carboxylesterase 1 (CES1) genetic variation on the activation of angiotensin-converting enzyme inhibitor (ACEI) prodrugs. In vitro incubation study of human liver, intestine and kidney s9 fractions demonstrated that the ACEI prodrugs enalapril, ramipril, perindopril, moexipril and fosinopril are selectively activated by CES1 in the liver. The impact of CES1/CES1VAR and CES1P1/CES1P1VAR genotypes and diplotypes on CES1 expression and activity on enalapril activation was investigated in 102 normal human liver samples. Neither the genotypes nor the diplotypes affected hepatic CES1 expression and activity. Moreover, among several CES1 nonsynonymous variants studied in transfected cell lines, the G143E (rs71647871) was a loss-of-function variant for the activation of all ACEIs tested. The CES1 activity on enalapril activation in human livers with the 143G/E genotype was approximately one-third of that carrying the 143G/G. Thus, some functional CES1 genetic variants (for example, G143E) may impair ACEI activation, and consequently affect therapeutic outcomes of ACEI prodrugs.

[Diaphragm pacemaker: alternative for chronic ventilatory support]. / Diafragmapacemaker: alternatief voor chronische beademing.

Currently, more than 2200 patients in the Netherlands receive chronic ventilatory support. In the majority of patients this leads to increased survival without any complications. Nevertheless, in case of ventilatory support via a mask, problems such as skin irritation, leakage and claustrophobia can occur. In case of tracheostomy, it can lead to increased pulmonary secretion. Diaphragm pacing with an external pacemaker might be an attractive alternative to prevent these symptoms as it can replace ventilatory support by mask or tracheostomy. Current indications are patients with spinal cord injury or with congenital central hypoventilation syndrome who are chronically respiratory insufficient. In our experience, patients can be completely or partially weaned from mechanical ventilation when using the diaphragm pacer. In the Netherlands, the technique is only performed at the University Medical Center Groningen.

['Trigger thumb' in 38 children: good short-term and long-term results from surgery]. / 'Knappende duim' bij 38 kinderen: goede resultaten van operatie op korte en lange termijn.

OBJECTIVE: To determine the direct and long-term effectivity of incision of the pulley in a trigger thumb (tendovaginitis stenosans). DESIGN: Retrospective study with follow-up. METHODS: In the period 1984-1995, 38 children (24 boys and 14 girls) were diagnosed and operated on 45 trigger thumbs in the Onze Lieve Vrouwe Gasthuis (Amsterdam) and Medisch Centrum Alkmaar, the Netherlands. Data were obtained from notes, operation reports and review in follow-up, at least 2 years after the operation. RESULTS: The mean age of the children at the moment of surgery was 3 years and 2 months (range: 11 months-10.33 years). 39 out of 45 thumbs were reviewed. Four thumbs had limited postoperative function. Two of these had a revision operation. There was 1 thumb with a postoperative superficial infection. At follow-up all thumbs had maximal function. The nodule in the tendon, which was palpable in 43 out of 45 thumbs preoperatively, had (almost) disappeared in all 39 thumbs at follow-up. There was a family history of trigger thumb in 33% of the 33 patients with follow up. 18% had bilateral involvement of the thumbs. The 6 digits not included in follow-up had a normal function according to the last notes. CONCLUSION: The results of surgery in the short term are good, in the long term excellent. Few complications occur. Based on the findings, it seems advisable to operate on children with a trigger thumb if there is no spontaneous recovery within half a year. Trigger thumb is the result of a congenital tight pulley.

Four-color multiparameter DNA flow cytometric method to study phenotypic intratumor heterogeneity in cervical cancer.

BACKGROUND: Multiparameter DNA flow cytometry using a one-laser bench-top flow cytometer has been restricted to three different colors. The two laser FACSCalibur has recently been introduced, allowing four-color analysis. Therefore, we optimized and extended our three-color method (Corver et al., 1994, Corver et al. 1996) to a four-color analysis of phenotypic intra-tumor heterogeneity using a bench-top flow cytometer. METHODS: First, the effect of a range of different propidium iodide (PI) and TO-PRO-3 iodide (TP3) concentrations on the coefficient of variation (CV) of the DNA histograms was measured using paraformaldehyde-fixed lysolecithin-permeabilized peripheral blood lymphocytes (PBLs) and SiHa and HeLa cervical cancer cells. Second, labeling freshly isolated cervical cancers from solid tumors was optimized with a mixture of anti-keratin antibodies. Third, the FACSCalibur hardware was modified, thereby allowing the simultaneous measurement of allophycocyanin (APC) fluorescence (FL4) in combination with FL3 pulse processing (FL3-W vs. FL3-A). The optimized procedure was then applied to cell suspensions from four different human cervical cancers to study phenotypic intratumor heterogeneity. Cell suspensions were simultaneously stained for DNA (PI, fluorescence) and three cellular antigens: (a) the epithelial cell-adhesion molecule (Ep-CAM; APC fluorescence), (b) keratin (R-phycoerythrin [RPE] fluorescence) to identify the epithelial fraction, and (c) vimentin (fluorescein-isothiocyanate [FITC] fluorescence) to label stromal cells. RESULTS: Overall, PI produced better CVs than did TP3. The optimal concentration of PI was 50-100 microM for all cells tested. Average CVs were 1.76% (PBL), 3.16% (HeLa), and 2.50% (SiHa). Optimal TP3 concentrations were 0.25-2.0 microM. Average CVs were 2. 58% (PBL), 5.16% (HeLa), and 3.96% (SiHa). Inter- or intra-DNA stem line heterogeneity of Ep-CAM expression was observed in the keratin-positive fractions. Vimentin-positive, keratin-negative cells were restricted to the DNA diploid fraction. CONCLUSIONS: PI is a superior DNA stain to TP3 when using intact normal PBL and human cancer cells. Four-color high-resolution multiparameter DNA flow cytometry allows the identification of intratumor subpopulations using PI as DNA stain and FITC, RPE, and APC as reporter molecules. The FACSCalibur bench-top flow cytometer can be used for this purpose, allowing the application of this technique in clinical laboratories.

[Orthopnea: not always of cardiac origin]. / Orthopneu: niet altijd cardiaal bepaald.

Respiratory insufficiency developed in a man aged 68 after cardiac surgery and in a man aged 60 with COPD and a history of cigarette smoking after an attack of 'flu', while in a woman aged 70 with non insulin-dependent diabetes mellitus it had been present for years. All three had bilateral diaphragmatic paralysis. The diagnosis is based on the triad orthopnoea, paradoxical abdominal movements during respiration in the recumbent position and a decrease of the vital capacity in the horizontal as compared with the sitting position. The patients' physical condition could be improved with the aid of (noninvasive) ventilatory support.

Waste gas monitor reduces wasted volatile anesthetic.

OBJECTIVE: The increasing focus on health care costs requires that all physicians evaluate practice behaviors. The primary emphasis in anesthesia has been limiting the use of expensive medications and interventions. Reducing waste is another approach, and volatile anesthetics are an appropriate target in that simple reduction of fresh gas-flow (FGF) rates is effective. A monitor that measures and displays the cost of wasted volatile anesthetic was developed and used to determine if real-time display of the cost would result in decreased FGF rates, which, in turn, would decrease wasted anesthetic. METHODS: The waste gas monitor (WGM) measures flow rate at the anesthesia machine's scavenger port, integrates this with agent concentration, and displays the calculated cost, real-time, on a portable computer screen. The WGM equipment was attached to the anesthesia machine in the gynecologic surgery operating room (OR) and those cases performed under general endotracheal anesthesia and lasting longer than one hour were eligible for inclusion. First year anesthesiology residents assigned to the study OR as part of a non-specialty rotation, were the subjects of the study. For each resident, after data were collected from at least two eligible baseline cases (Baseline Phase, WGM not visible and resident unaware of its presence), the monitor was introduced and data collection continued for at least three more eligible cases (Visible Phase). RESULTS: Nine residents were initially enrolled, but due to scheduling difficulties only five residents completed the protocol. Data from cases using the WGM demonstrated a 50% decrease (3.58 +/- 1.34 l/min vs. 1.78 +/- 0.51 l/min (p = 0.009)) in the scavenger flow rates, which resulted in a 48% ($5.28 +/- 0.68 vs. $2.72 +/- 0.80 (p = 0.002)) decrease in hourly cost of wasted volatile anesthetic. There was no difference between the Baseline and Visible phases with regard to use of nitrous oxide or intravenous anesthetic agents. CONCLUSIONS. The WGM decreased wasted volatile anesthetic by encouraging decreased FGF rates.

Autoregulation in a simulator-based educational model of intracranial physiology.

OBJECTIVE: To implement a realistic autoregulation mechanism to enhance an existing educational brain model that displays in real-time the cerebral metabolic rate (CMRO2), cerebral blood flow (CBF), cerebral blood volume (CBV), intracranial pressure (ICP), and cerebral perfusion pressure (CPP). METHODS: A dynamic cerebrovascular resistance (CVR) feedback loop adjusts automatically to maintain CBF within a range of the CPP and defines autoregulation. The model obtains physiologic parameters from a full-scale patient simulator. We assumed that oxygen demand and arterial partial pressure of carbon dioxide (CO2 responsivity) are the two major factors involved in determining CBF. In addition, our brain model increases oxygen extraction up to 70% once CBF becomes insufficient to support CMRO2. The model was validated against data from the literature. RESULTS: The model's response varied less than 9% from the literature data. Similarly, based on correlation coefficients between the brain model and experimental data, a good fit was obtained for curves describing the relationship between CBF and PaCO2 at a mean arterial blood pressure of 150 mm Hg (R2 = 0.92) and 100 mm Hg (R2 = 0.70). DISCUSSION: The autoregulated brain model, with incorporated CO2 responsivity and a variable oxygen extraction, automatically produces changes in CVR, CBF, CBV, and ICP consistent with literature reports, when run concurrently with a METI full-scale patient simulator (Medical Education Technologies, Inc., Sarasota, Florida). Once the model is enhanced to include herniation, vasospasm, and drug effects, its utility will be expanded beyond demonstrating only basic neuroanesthesia concepts.

A computer model of intracranial dynamics integrated to a full-scale patient simulator.

The ability to visualize intracranial dynamics during simulated clinical scenarios is a valuable tool for teaching brain physiology and the consequences of different medical interventions on the brain. Studies have isolated physiologic variables and shown their effects on brain dynamics. However, no studies have shown the combined effects of these variables on intracranial dynamics. This brain model offers one approach that brings all these relationships together and shows how they affect the dynamics of the brain. The brain model obtains its physiologic inputs from a full-scale patient simulator which responds to clinical interventions. This integration allows individuals working on the patient simulator to see the effects of their actions on brain dynamics. The brain model gives a real-time display of intracranial events (cerebral metabolic rate, cerebral blood flow, cerebral blood volume, cerebral perfusion pressure, and intracranial pressure) and responds to changes in the pulmonary and cardiovascular condition of the patient simulator.

Transient osteoporosis and osteogenesis imperfecta. A case report.

The authors report migratory transient osteoporsis of the ipsilateral hip and ankle in a patient with ostengenesis imperfecta. The diagnosis was made with modern imaging techniques (magnetic resonance imaging, bone scintigraphy, and dual energy xray absorptiometry). Histologic examination after bone biopsy of the proximal femur showed possible microfractures. The treatment consisted of a regimen of nonweightbearing. One year after onset, the patient had no symptoms and no residual evidence of transient osteoporosis on radiographic studies. The etiology of transient osteoporosis in patients who have osteogenesis imperfecta is uncertain. The authors' findings suggest that microfractures may play a role in the early pathophysiologic process.

Computerized pre-anesthetic evaluation results in additional abstracted comorbidity diagnoses.

OBJECTIVE: To study the impact of information from a physician-entry computerized preanesthetic evaluation system on the coding of International Classification of Diseases (ICD-9-CM) diagnoses and on hospital reimbursement due to alterations in diagnosis-related group (DRG) codes. METHODS: Nonrandomized, unblinded trial conducted at a 570-bed university tertiary care hospital. First without and then with reference to information contained on computer-based preanesthetic evaluation reports, medical charts were coded by the study institution's usual professional codes for ICD-9-CM discharge diagnoses and DRG assignment. RESULTS: For 22 of 180 charts studied (12%, 95% confidence limits 7.4% to 16.7%), at least one ICD-9-CM diagnosis was added. Three of 84 DRG-based reimbursements were altered, increasing hospital reimbursement by 1.5%. CONCLUSIONS: Supplemental information from a physician-entered, problem-oriented, computerized preanesthetic evaluation system improved discovery of diagnoses in the population studied.

Positive end-expiratory pressure and lung compliance: effect on delivered tidal volume.

The effects of positive end-expiratory pressure (PEEP) and lung compliance (CL) on delivered tidal volume (VTdel) and ventilator output were evaluated in the following anaesthesia machine/ventilator systems: Narkomed III with a Model AV-E ventilator (III/AV-E system) and an Ohmeda Modulus II with either a 7810 anaesthesia ventilator (II/7810 system) or a Model 7000 anaesthesia ventilator (II/7000 system). With a standard circle anaesthesia breathing circuit connected to a test lung simulating CL, gas flow was measured and integrated over time at each combination of VT settings (VTset), 500 ml or 1000 ml; CL settings, 0.15 to 0.01 L.cm H2O-1 decreased incrementally; and PEEP settings, 0 to 30 cm H2O increased in 5-cm H2O increments. The integral of gas flow at the Y-piece of the breathing circuit was recorded as VTdel and at the output of the ventilator bellows as ventilator output. As CL decreased to 0.01 L.cm H2O-1 and PEEP increased to 30 cm H2O, at VTset of 500 ml and 1000 ml, respective VTdel decreased linearly to 251 +/- 6 ml and 542 +/- 7 with the III/AV-E, 201 +/- 5 and 439 +/- 5, with the II/7810, and 181 +/- 4 and 433 +/- 7 ml with the II/7000 (P < 0.05 among the three systems). Loss in VTdel due to PEEP alone, which increased only slightly when VTset was increased, accounted for an increasingly greater percentage of VTset as it was decreased, which was less pronounced with low CL.(ABSTRACT TRUNCATED AT 250 WORDS)

Computer-modulated patient-controlled analgesia. Preliminary evaluation of a prototype.

BACKGROUND AND OBJECTIVES: To provide patients with better postoperative pain relief, the authors developed a prototype computer-controlled infusion pump capable of establishing a steady drug plasma concentration based on patient needs. METHODS: A two-compartment pharmacokinetic model was used to compute the required infusion scheme. Using known pharmacokinetic parameters, the model and the pump's accuracy were studied in four dogs. In the first part of the study, the morphine pharmacokinetic profile of each dog was analyzed and used to develop the parameters of a model tailored to that particular dog. In the second part, this tailored model was implemented to test whether the infusion device was able to achieve the desired concentration profile. RESULTS: The computer-controlled infusion device was able to achieve all the desired plasma concentrations. CONCLUSIONS: These data suggest that it is possible to refine postoperative pain management with adaptive computer algorithms implemented to establish stable plasma analgesic concentrations and to automatically wean the analgesic over time.

The efficiency of preoperative evaluation: a comparison of computerized and paper recording systems.

OBJECTIVE: We designed and implemented a preoperative evaluation record system with seven networked computers for use by physicians and other medical staff. This study compared the efficiency of the new computerized system with that of the paper system. METHODS: We reviewed data from preoperative evaluations completed from November 1990 through December 1992. Data were analyzed automatically (Borland C program) for two intervals: (1) the waiting period, defined as the time the patient entered the waiting room until he or she entered the examination room; and (2) the examination period, defined as the time the patient entered the examination room until an evaluation form was printed. Data were obtained for 2,511 evaluations on paper and 8,342 by computer. RESULTS: The average waiting period with the paper system was 56.1 +/- 44.8 min; the average waiting period with the computerized system was 59.1 +/- 47.0 min. The average examination period was nearly identical for both systems: 27.5 +/- 23.6 min for the paper system; 28.5 +/- 22.7 min for the computerized system. CONCLUSION: The computerized system required no more examination time than the manual system. In addition, we speculate that time is saved at other points of patient care by the legible, instantly retrievable preoperative evaluations that the computerized system produces.

Alarms and their limits in monitoring.

The need to incorporate alarms in monitoring systems is related to the growing complexity of monitoring and the large number of variables. For sophisticated alarms, information about the inputs to the patient is of importance; for example, clinical interventions such as drug administration and ventilation readjustment need to be known to the monitoring system. Alarms are triggered by signals or signal features that exceed thresholds. Each threshold must be seen as a level that needs to be set, either manually or automatically. The large number of levels to be set creates an extra workload for the clinician. Approaches to determine such levels automatically are discussed in this article. Most promising seems the multiple signal approach using an expert system. It seems reasonable to expect that information concerning alarm limits, needed for the operation of knowledge-based alarm systems, may come from integrated departmental data bases.

Comparative potency of atropine sulphate and glycopyrrolate on heart rate in man.

Disagreement as to the effect of glycopyrrolate and atropine sulphate at various dosages on heart rate has been reported in the literature. Of particular interest is the question of whether small doses of glycopyrrolate cause bradycardia. Three groups of subjects were studied. The QRS complexes of the electrocardiogram were continuously recorded on a microcomputer. Group 1 consisted of 10 healthy volunteers who were given two doses of atropine sulphate 1.25 micrograms kg-1 and glycopyrrolate 0.75 micrograms kg-1, in random order at two different times, i.v. Monitoring continued until heart rate returned to baseline. Group 2 consisted of 24 women, ASA class I or II, scheduled for gynaecological operations. Each patient received fractionated i.v. doses of either atropine sulphate 2.5, 2.5 and 5 micrograms kg-1 or glycopyrrolate 1.5, 1.5 and 3.0 micrograms kg-1 at 3-min intervals. Heart rate was measured continuously for 1 h before drug injection and for 10 min after the last dose. Group 3 consisted of six volunteers given both drugs in the same dose and time schedule as Group 2, but heart rate was monitored for 180 min after the last dose. In Group 1, the incidence of bradycardia and increases in heart rate after the first dose were statistically significant for both atropine sulphate and glycopyrrolate when compared with baseline values. In Group 2, both drugs significantly increased the heart rate and had similar times to peak effect. In Group 3, bradycardia occurred only with atropine sulphate. Increases in heart rate, peak heart rate and duration of action were similar with both drugs.(ABSTRACT TRUNCATED AT 250 WORDS)