[Tests for alcohol consumption during pregnancy: what biomarkers are suitable?]. / Testen op alcoholgebruik in de zwangerschap.

Alcohol consumption during pregnancy may lead to severe foetal damage, such as foetal alcohol spectrum disorders. It is known that pregnant women under-report to questionnaires about alcohol consumption. It is therefore necessary to determine alcohol consumption during pregnancy objectively. We present 2 pregnant women with negative urine tests for ethyl glucuronide (EtG) and alcohol. However, analysis of two other biomarkers, phosphatidylethanol (PEth) in blood and fatty acid ethyl esters (FAEE) in meconium, revealed alcohol consumption during pregnancy by both women. Analysis of PEth can yield additional information alongside EtG testing. This is due to the much longer half-life of PEth. Meconium testing for FAEE provides relevant information about alcohol consumption during the second and third trimesters. Both PEth and meconium analysis can help identify women who have consumed alcohol during pregnancy. Appropriate counselling and follow-up can be given to these mothers and their children.

[Caesarean section in conflict with the patient's right to self-determination?]. / Een sectio caesarea tegen haar wil?

Competent patients have the right to refuse treatment and healthcare workers should acknowledge their wishes. In the Netherlands there are conflicting (constitutional) rights of the foetus and of mentally ill patients. This paper describes the legal and ethical problems in the case of a mentally ill patient at 37 weeks of pregnancy who refused an obstetric examination. The patient refused to cooperate and have her physical condition and mental status examined. Her refusal endangered the life of the foetus. The obstetrician decided to perform a caesarean section, even if this would be in conflict with the patient's right to self-determination. In these cases no legal framework exists for providing the best medical care. New legislation should be drawn up to prevent similar cases occurring in the future. If a caesarean section is in conflict with a patient's right to self-determination, it should always be performed as a last resort.

Perceived sleep quality is worse than objective parameters of sleep in pregnant women with a mental disorder.

OBJECTIVE: Disturbed sleep during pregnancy is associated with adverse obstetric outcomes and less mental well-being. In pregnant women with a mental disorder, who frequently suffer from sleep problems, it is unknown whether predominantly objective or subjective sleep quality is more affected. To clarify this, we compared objective and subjective parameters of sleep quality between patients and healthy controls during pregnancy. METHODS: This observational study was embedded in an ongoing study among pregnant women with a mental disorder at the department of Psychiatry of Erasmus University Medical Center Rotterdam, the Netherlands. We compared 21 pregnant women with a confirmed mental disorder with 33 healthy controls (gestational age, 23-29 weeks). To measure objective parameters of sleep quality, all participants continuously wore a wrist actigraph for 7 days and nights. Subjective sleep quality was retrospectively assessed using the Pittsburgh Sleep Quality Index (PSQI) and on a daily basis with the Subjective Sleep Quality-scale (SSQ). Differences in parameters of sleep between patients and controls were tested using a multivariate linear regression analysis adjusted for parity, gestational age, educational level, and employment status. RESULTS: Objective parameters of sleep quality and subjective sleep quality as assessed by the PSQI did not differ significantly between patients and controls. Daily sleep reports showed that, relative to controls, patients had a significantly worse average SSQ-score (5.2 vs. 7.6, adjusted ß = 0.12, 95%CI = 0.03-0.53, p < 0.01). CONCLUSIONS: Our exploratory study suggests that perceived sleep quality reported on a daily basis by pregnant women with a mental disorder is worse than the sleep quality as measured by wrist actigraphy.

The feasibility of incorporating structured therapeutic consultations with real patients into the clinical clerkship internal medicine.

This study aims to determine the feasibility of incorporating structured therapeutic consultations (TCs) into the clinical clerkship internal medicine. TCs were considered feasible if students were able to draw up a therapeutic plan and carry out a TC, and if students and their supervisors considered TCs workable and useful. From March 2008 to October 2009, medical students carried out a "diagnostic" and subsequent "therapeutic" consultation with the same patient during their clinical clerkship internal medicine at the VU University Medical Center. After the diagnosis was established, the student had to formulate a therapeutic plan and then carry out a TC with the patient, supervised by a clinician. The supervisor assessed the therapeutic plan and how the student conducted the TC. Both the student and the supervisor received a questionnaire about the workability and usefulness of the TC. On average, students' performance in drawing up a therapeutic plan was awarded a score of 4.4 on a five-point scale, and the TC performance of 96 % of the students was considered amply sufficient or better. Eighty-three percent of the supervisors agreed or strongly agreed with the statement that the TC is a worthwhile addition to the clerkship, and 67 % of the students indicated that they would like to perform more TCs. This study shows that incorporating a structured TC with a real patient into the clinical clerkship internal medicine is both feasible and worthwhile. This may be an important step to improving the prescribing skills and attitudes of junior doctors and residents and to reducing their prescribing errors after graduation.

The relationship between arterial PO2 and mixed venous PO2 in response to changes in positive end-expiratory pressure in ventilated patients.

The response of arterial PO(2) (P(a)O(2)) to airway pressure has been used as a measure of recruitment in mechanically ventilated patients. We hypothesised that mixed venous PO(2) (P(mv)O(2)) directly affects P(a)O(2). Sixteen patients with acute lung injury (ALI, lung injury score > or = 1) on volume-controlled mechanical ventilation (F(I)O(2) 0.40) were studied. Positive end-expiratory pressure (PEEP) was increased and decreased. Incremental PEEP increased median values of P(a)O(2), diminished venous admixture (Q(va)/Q(t)) and cardiac index, but maintained arterial PCO(2) and tissue O(2) uptake. These changes were reversed during decremental PEEP. However P(a)O(2) did not increase in 37% of PEEP steps and changes in P(a)O(2) correlated to those in P(mv)O(2) (r(s) = 0.45, p < 0.001). Changes in P(mv)O(2) contributed to changes in Q(va)/Q(t) in determining changes in P(a)O(2) (p < 0.05). P(mv)O(2) may be an independent determinant of P(a)O(2) during mechanical ventilation for ALI, so that dosing PEEP to recruit the lung should not be guided by arterial blood oxygenation alone. Arterial hypoxaemia with increasing PEEP may improve by reducing PEEP (or increasing tissue O(2) delivery), when the fall in P(mv)O(2) is greater than about 0.133 kPa.

The anatomical limits of the posterior vaginal vault toward its use as route for intra-abdominal procedures.

BACKGROUND: The use of natural openings for abdominal surgery started at the beginning of the 21st century. A trans-Douglas endoscopic device has been designed to perform most of the intra-abdominal operations in women through the pouch of Douglas. The posterior vaginal vault is limited in size and could be damaged by an oversized instrument. This study investigates the optimal dimensions of the instrument by measuring the limiting factor in the passage. METHODS: In ten female embalmed bodies the transversal and sagittal diameter of the fornix posterior vaginalis was measured by two observers. The pouch of Douglas was filled to its maximal capacity with mouldable latex through an open abdomen. By internal vaginal examination the connective tissue borders of the fornix posterior were palpated and the impression in the cast was measured. The mean value of these two diameters was evaluated in this study. The level of agreement between the observers was calculated. RESULTS: The mean fornix posterior diameter was 2.6 cm (standard deviation, SD 0.5 cm) with a range of 2.0-3.4 cm. The mean difference between the two observers of all measurements was 0.08 cm (not significant). Both observers had an acceptable intraobserver variation. The interobserver agreement was excellent. CONCLUSION: Instruments with dimensions within the measured limits can be used safely for intra-abdominal operations via the natural orifice of the vagina.

A context-learning pharmacotherapy program for preclinical medical students leads to more rational drug prescribing during their clinical clerkship in internal medicine.

The irrational prescribing of drugs seems to be a general problem in medical practice, occasionally leading to serious consequences. In order to improve the drug prescribing performance of medical students, a compulsory context-learning pharmacotherapy module was implemented in 1998 in the medical curriculum of 2nd-4th-year medical students at theVU University Medical Center (VUmc), Amsterdam, The Netherlands. As part of this program, preclinical medical students are taught how to select, prescribe, and evaluate a drug regimen rationally. The aim of this study was to investigate the effect of this preclinical pharmacotherapy program on the quality of rational prescribing during the ensuing clinical clerkship of these students in internal medicine. The results of this study indicate that preclinical context-learning in pharmacotherapy leads to the use of more rational prescribing modalities by medical students during their ensuing clinical clerkship in internal medicine. This effect was obtained not only with respect to the clinical topics in which training had been given as part of the pharmacotherapy curriculum, but also for other disease situations that the students dealt with. This implies that students not only remember the specific information they have learned during the training, but are also able to apply the acquired skills in new situations (transfer effect).

[First abdominal access in gynecological laparoscopy: which method to utilize?]. / Primo accesso addominale in laparoscopia ginecologica: quale tecnica utilizzare?

The choice of the technique to enter the peritoneal cavity, during a laparoscopy, depends on a lot of variables which hinder a standardized method and, actually, it appears impossible to show, with certainty, the best method to choose for the first abdominal access in gynecological laparoscopy. The preference for one or another technique depends on the operator experience, school and speciality of the surgeon, laparoscopical upgrading and the work environment; many surgical techniques are not yet used due the limits and fears of some surgeons to change the preference in first access approaching and for the lack of operating versatility by a method or another one. A review of the scientific literature, underlines that the major problems during the first laparoscopical abdominal access are two, vascular and intestinal and their percentage is variable. In this paper we describe the large range of methods for open and closed laparoscopy and for direct access, that permit to perform a first abdominal laparoscopical access, and their major possible problems.

[Pregnant, addicted prostitutes: compulsory admission is sometimes necessary in the interests of the child]. / Zwangere, verslaafde prostituees: soms gedwongen opname in het belang van het kind.

Three drug-addicted prostitutes, who were 37, 27 and 25 weeks pregnant respectively, were admitted to a psychiatric department under court order. After the birth, the children were placed in foster families. The mothers withdrew from further treatment. In Rotterdam, The Netherlands, there is a city network made up of doctors and social workers; in the case of addicted pregnant prostitutes they advise the Child Protection Agency of the Ministry of Justice about the care of the child after its birth. The combination of heavy addiction and prostitution in a pregnancy without any prenatal care can be considered a psychiatric disorder. Consequently, an addicted woman can be compulsorily admitted because of the threat she forms to her unborn child. In these cases the mother's right to self-determination must be limited in the interest of the child.

Effect of the mechanical ventilatory cycle on thermodilution right ventricular volumes and cardiac output.

The purpose of this study was to evaluate right ventricular (RV) loading and cardiac output changes, by using the thermodilution technique, during the mechanical ventilatory cycle. Fifteen critically ill patients on mechanical ventilation, with 5 cmH(2)O of positive end-expiratory pressure, mean respiratory frequency of 18 breaths/min, and mean tidal volume of 708 ml, were studied with help of a rapid-response thermistor RV ejection fraction pulmonary artery catheter, allowing 5-ml room-temperature 5% isotonic dextrose thermodilution measurements of cardiac index (CI), stroke volume (SV) index, RV ejection fraction (RVEF), RV end-diastolic volume (RVEDV), and RV end-systolic volume (RVESV) indexes at 10% intervals of the mechanical ventilatory cycle. The ventilatory modulation of CI and RV volumes varied from patient to patient, and the interindividual variability was greater for the latter variables. Within patients also, RV volumes were modulated more by the ventilatory cycle than CI and SV index. Around a mean value of 3.95 +/- 1.18 l. min(-1). m(-2) (= 100%), CI varied from 87.3 +/- 5.2 (minimum) to 114.3 +/- 5.1% (maximum), and RVESV index varied between 61.5 +/- 17.8 and 149.3 +/- 34.1% of mean 55.1 +/- 17.9 ml/m(2) during the ventilatory cycle. The variations in the cycle exceeded the measurement error even though the latter was greater for RVEF and volumes than for CI and SV index. For mean values, there was an inspiratory decrease in RVEF and increase in RVESV, whereas a rise in RVEDV largely prevented a fall in SV index. We conclude that cyclic RV afterloading necessitates multiple thermodilution measurements equally spaced in the ventilatory cycle for reliable assessment of RV performance during mechanical ventilation of patients.

[Syphilis in addicted pregnant women: better care through more awareness and contract between organizations involved]. / Syfilis bij de verslaafde zwangere: betere zorg mogelijk door meer alertheid en meer contact tussen betrokken instellingen.

Three women, aged 21, 20 and 30 years, were cocaine users and pregnant. There had been no prenatal monitoring until they reported with uterine contractions. Blood of the first two women was then tested; serology revealed active syphilis infections: their children had died in utero. The blood of the third woman had been tested as part of a street project; it revealed an active syphilitic infection but she could not be found for treatment. After delivery, the child showed withdrawal symptoms. The first and third women and the child of the third woman were treated with benzylpenicillin. The system for screening and treating drug-addicted pregnant women should be intensified.

Three distinct D-amino acid substitutions confer potent antiangiogenic activity on an inactive peptide derived from a thrombospondin-1 type 1 repeat.

Mal II, a 19-residue peptide derived from the second type 1 properdin-like repeat of the antiangiogenic protein thrombospondin-1 (TSP-1), was inactive in angiogenesis assays. Yet the substitution of any one of three L-amino acids by their D-enantiomers conferred on this peptide a potent antiangiogenic activity approaching that of the intact 450-kDa TSP-1. Substituted peptides inhibited the migration of capillary endothelial cells with an ED50 of 8.5 nM for the D-Ile-15 substitution, 10 nM for the D-Ser-4 substitution, and 0.75 nM for the D-Ser-5 substitution. A peptide with D-Ile at position 15 could be shortened to its last seven amino acids with little loss in activity. Like whole TSP-1, the Mal II D-Ile derivative inhibited a broad range of angiogenic inducers, was selective for endothelial cells, and required CD36 receptor binding for activity. A variety of end modifications further improved peptide potency. An ethylamide-capped heptapeptide was also active systemically in that when injected i.p. it rendered mice unable to mount a corneal angiogenic response, suggesting the potential usefulness of such peptides as antiangiogenic therapeutics.

"Helper:" A critical events prompter for unexpected emergencies.

OBJECTIVE: The medical practitioner is faced with an increasing list of protocols and algorithms related to patient care. These recommendations are often difficult to recall, particularly in stressful emergency situations. Using advanced cardiac life support (ACLS) protocols, we built a computer-based system to exhibit precompiled response plans for medical emergencies. To validate the usefulness of this prompting device, we tested application of two of the nine ACLS algorithms, pulseless ventricular fibrillation/ventricular tachycardia (Vfib/Vtach) and bradycardia, in a simulated operating room (OR) environment. METHODS: The system utilized the software authoring system IconAuthor (Aimtec Inc., Nashua, NH) and a touch-screen monitor (DiamondScan, Microtouch, Methuen, MA). Prior to testing our system, all 39 subjects were given time to familiarize themselves with its operation. Subsequently, all subjects were videotaped while managing a standard simulated anesthetic. During the anesthetic, the subjects were presented with two emergency scenarios, not viewed during the familiarization period. The electrocardiographic (EKG) signals for normal sinus rhythm, ventricular fibrillation, and second-degree heart block were presented. By random selection, the prompter was available to half of the subjects for help with arrhythmia management (experimental group), while to half it was not (control group). RESULTS: A total of 39 subjects completed the exercise. Use of the prompter enabled significantly more subjects to administer correct drugs and dosages during ventricular fibrillation. The correct lidocaine dose was chosen more often by the experimental group than by the control (p = 0.015); similarly MgSO4 was appropriately ordered more often in the experimental group (p = 0.003). During second-degree heart block, atropine was correctly followed with a dopamine infusion (p = 0.004), and epinephrine infusion was ordered for refractory bradycardia (p = 0.002) more often in the experimental than the control group. CONCLUSIONS: These data demonstrate the value of a prompting device at the anesthesia workstation. We foresee the use of such prompters in many areas of medicine.

Transient increase in interleukin-8 and pulmonary microvascular permeability following aortic surgery.

Aortic surgery results in ischemia/reperfusion of the lower body. This may liberate inflammatory mediators that activate neutrophils, and may result in lung microvascular changes with increased permeability and respiratory failure. We studied circulating inflammatory mediators and the pulmonary leak index (PLI) of 67Ga, a measure of transvascular transferrin transport and permeability, in patients scheduled for elective aortic and peripheral vascular surgery, before and after surgery. Aortic surgery patients in Groups 1 (n = 10) and 2 (n = 7) were studied before and at a median of 2.5 and 21.0 h after surgery, respectively. A control Group 3 (n = 6) was studied before and at a median of 2.9 h after peripheral vascular surgery. The PLI (median) increased from a median of 9.1 (range, 6.6 to 14.7) before to a median of 23.4 (range, 18.7 to 86.4) x 10(-3)/min after surgery in Group 1 but not in the other groups (p < 0.001). The postoperative increase in circulating neutrophils and elastase-alpha 1-antitrypsin, a marker of neutrophil activation, was similar among the groups. Plasma levels of activated complement 3a and tumor necrosis factor (TNF-alpha) did not change in any of the groups. In contrast, plasma levels of interleukin-8 (IL-8) increased in Group 1 from < 3 (range, < 3 to 37) before to 324 (range, 36 to 868) pg/ml after surgery, but did not change in the other groups (p < 0.005). The decrease in plasma levels of angiotensin converting enzyme (ACE) was greater in Group 1 than in the other groups (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute effect of ibopamine and isosorbide mononitrate on blood volume distribution in congestive heart failure.

In order to compare ibopamine (IBO), a dopamine congener, with isosorbide mononitrate (ISMN) and to study their interaction in effects on the capacitance vasculature in congestive heart failure (CHF), a prospective, randomized, placebo-controlled, double-blind clinical trial was performed in 32 patients with New York Heart Association class II-IV CHF, randomly assigned to receive single oral doses of placebo, 200 mg IBO, 20 mg ISMN, or both IBO and ISMN. After labelling of red cells with 99mTc, changes in regional radioactivity, indicative of changes in blood volume, were recorded using a gamma-camera before and at 30, 60 and 120 min after drug administration. At 30 and 60 min, arterial systolic and pulse pressures were higher with IBO than with ISMN and placebo (for pulse pressure by mean 13.7 mmHg, 95% confidence interval 4.5-23.0 mmHg, at 30 min), probably reflecting an IBO-induced rise in stroke volume at unchanged heart rate and mean arterial pressure. IBO did not change regional radioactivity except for a transient increase of 4.4% (0.5-7.6%) in the thorax at 30 min. This was attenuated by concomitant ISMN treatment since, starting at 30 min, the drug increased radioactivity in the legs, compared with patients not receiving the drug, by 8.0% (95% confidence interval 0.2-15.8%), leading to a fall in thoracic and left ventricular radioactivity at 30 min of 3.4% (0.3-7.0%) and 6.4% (0.8-11.9%), respectively, and a fall of 5.5% (0.5-10.5%) in hepatic radioactivity at 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Transvascular transport of 67Ga in the lungs after cardiopulmonary bypass surgery.

STUDY OBJECTIVE: To examine the effect of cardiac surgery with cardiopulmonary bypass (CPB) on pulmonary vascular permeability. DESIGN: A prospective, serial study. SETTING: Department of nuclear medicine and intensive care units of a university hospital. PATIENTS: Twelve consecutive patients were studied, before and immediately after elective cardiac surgery using CPB (group 1), and 4 consecutive, artificially ventilated patients with acute cardiogenic pulmonary edema (group 2). MEASUREMENTS AND RESULTS: The kinetics in blood and over both lungs were measured, using two mobile probes at the bedside, of intravenously injected 67Ga, assumed to bind to circulating transferrin, and in vitro 99mTc-labeled red blood cells to account for pulmonary blood volume. From data recorded in time (1 h), a pulmonary leak index (PLI), the time constant of transport of 67Ga from the intravascular to the extravascular space of the lung, was calculated and values for both lungs were averaged. In group 1, the PLI (.10(-3).min-1, mean +/- SD) was 8.2 +/- 3.7 before and 17.0 +/- 13.5 after CPB surgery (p < 0.01) and changes directly related to the duration of CPB. In four patients with a CPB duration > or = 120 min, the PLI, 31.1 +/- 16.3.10(-3).min-1, exceeded 2 SD plus mean preoperative PLI. Changes in PLI tended to relate inversely to changes in arterial WBC, which, in turn, inversely related to CPB duration. The PaO2/FIO2 ratio decreased and tended to relate inversely to PLI after surgery. No patient developed alveolar pulmonary edema on chest radiograph. In group 2, the PLI was 11.1 +/- 3.1.10(-3).min-1 (NS from group 1 preoperative PLI). CONCLUSIONS: Cardiopulmonary bypass induces a pulmonary vascular leak, as assessed by 67Ga kinetics using a bedside detection technique, in some cardiac surgery patients with prolonged CPB. This leak may reflect pulmonary vascular injury and increased permeability, following activation of leukocytes by CPB and subsequent pulmonary sequestration, rather than increased filtration through pressure factors. It may contribute to impaired gas exchange, even in the absence of manifest alveolar edema of the lungs, after surgery.