Ethyl glucuronide (EtG): better than breathalyser or self-reports to detect covert short-term relapses into drinking.

AIMS: The assessment of relapses is widely used as an outcome measure of alcohol dependence treatment. However, the methods of assessing relapses range from questionnaires to biological markers of alcohol for different time spans. The aim of this study was to compare the relapse rates of weekend home stays during long-term alcohol dependence treatment, assessed by ethyl glucuronide (EtG), breath alcohol tests and self-reports. METHODS: Two hundred and ninety-seven alcohol-dependent patients receiving a long-term inpatient treatment programme participated. After a weekend at home (Friday to Sunday) they were evaluated for relapse by personal interviews and with breath alcohol tests. A concomitantly collected urine sample was later assessed for EtG with liquid chromatography-tandem mass spectrometry (LC-MS/MS analysis). RESULTS: Of the total, 37.7% of the patients were positive for EtG at least once. Breath alcohol tests had been positive in only 4.4% and in personal interviews only 5.7% of the patients had admitted relapse. 15.6% of EtG tests were positive, but breath alcohol tests were negative (Cohen's kappa = 0.056). Ninety-three per cent of the relapses were only detected by EtG. CONCLUSION: In addition to breath alcohol tests and interviews, urinary EtG can clearly improve the verification of relapse in inpatient treatment programmes allowing for weekend stays at home. Without EtG testing, a high amount of relapses will stay undetected.

Alpha-1-Fetoprotein (AFP): international proficiency study with different test systems.

BACKGROUND: The present proficiency study aimed to elucidate the comparability and reliability of test systems for the determination of AFP concentrations. METHODS: 25 laboratories using 8 different commercial test systems used liquid BIOREF-AFP control serum in their routine internal quality control over a period of one year. For statistical analysis the results were collected centrally. RESULTS: The statistical analysis of the test results revealed considerable variation for the different laboratories. The deviations of the mean values of different laboratories from the overall mean value varied between 0.1 and 26.1%, and for most of the laboratories the deviation was round about 10%. The precision of measured values in the individual laboratories was in most cases acceptable: Nevertheless, the coefficients of variation of the individual laboratories ranged from 13 to 16.1%. CONCLUSIONS: In conclusion, this study indicates that AFP results vary between different laboratories albeit an international standard for AFP is available. Therefore, every laboratory should participate in external ring studies and should use a quality control serum independent of the test kit manufacturer for the internal quality control.

Blood gas partition coefficient and pulmonary extraction ratio for propofol in goats and pigs.

The interpretation of continuously measured propofol concentration in respiratory gas demands knowledge about the blood gas partition coefficient and pulmonary extraction ratio for propofol. In the present investigation we compared both variables for propofol between goats and pigs during a propofol anaesthesia. In ten goats and ten pigs, expired alveolar gas and arterial and mixed venous blood samples were simultaneously drawn during total intravenous anaesthesia with propofol. The blood gas partition coefficient and pulmonary extraction ratio were calculated for both species. Non-parametric methods were used for statistical inference. The blood gas partition coefficient ranged between 7000 and 646,000 for goats and between 17,000 and 267,000 for pigs. The pulmonary extraction ratio ranged between 32.9% and 98.1% for goats and was higher for pigs, which ranged between -106.0% and 39.0%. The blood gas partition coefficient for propofol exceeded those for other known anaesthetic compounds so that it takes longer to develop a steady-state. The different pulmonary extraction rates in two species suggest that there are different ways to distribute propofol during the lung passage on its way from the blood to breathing gas. This species-specific difference has to be considered for methods using the alveolar gas for monitoring the propofol concentration in plasma.

Propofol concentration in exhaled air and arterial plasma in mechanically ventilated patients undergoing cardiac surgery.

BACKGROUND: Measuring propofol concentration in plasma (c(P)PL) and in exhaled alveolar gas (c(P)G) during constant infusion provides information about their respective time courses. In the present study, we compared these time courses in patients undergoing cardiac surgery from the beginning of propofol anaesthesia until eye opening upon awakening. METHODS: The c(P)G was measured before, during, and after continuous infusion of propofol for general anaesthesia in 12 patients at two randomly allocated doses (3 or 6 mg kg(-1) h(-1)). Gas samples were collected on Tenax tubes. After thermodesorption, c(P)G was measured by gas chromatography mass spectrometry. Simultaneously with exhaled gas, arterial blood was sampled for measuring c(P)PL by reversed-phase high-performance liquid chromatography with fluorescence detection. In order to compare the time courses of c(P)PL and c(P)G as dimensionless values directly, each gas and plasma value was normalized by relating it to the corresponding value at the end of the initial infusion after 40 min. RESULTS: The c(P)G ranged between 2.8 and 22.5 ppb, whereas the corresponding c(P)PL varied between 0.3 and 3.3 microg ml(-1). Normalized concentration values showed a delayed increase in c(P)G compared with c(P)PL under constant propofol infusion before the onset of cardiopulmonary bypass, and a delayed decrease after stopping the propofol at the end of anaesthesia. CONCLUSIONS: Propofol can be measured in exhaled gas from the beginning until the end of propofol anaesthesia. The different time courses of c(P)PL and c(P)G have to be considered when interpreting c(P)G.

Topical treatment of ocular surface defects: comparison of the epitheliotrophic capacity of fresh frozen plasma and serum on corneal epithelial cells in an in vitro cell culture model.

Accelerated healing of ocular surface disorders was reported using serum for topical application. It is supposed that growth factors, fibronectin and vitamins in serum support the proliferation of corneal epithelial cells. The use of fresh frozen plasma (FFP) instead of serum is theoretically attractive, as it is more easily available from blood banks. In this study, serum and FFP were investigated for composition of epitheliotrophic factors and effect on corneal epithelial cells. Whole blood was taken from five donors. Serum and FFP were prepared, and the concentrations of epithelial growth factor (EGF), Platelet-derived growth factor (PDGF), transforming growth factor-beta1, fibronectin and vitamin A were determined. Immortalized human corneal epithelial cells were used to investigate growth, migration and differentiation in response to both blood products. Significant differences were found regarding the mediator composition of serum and FFP. Serum rather than FFP was significantly superior in stimulating cell growth, migration and differentiation. The epitheliotrophic capacity of blood products depends upon the composition of growth factors and vitamins. Blood clotting strongly influences the growth factor pattern. The superior epitheliotrophic capacity of serum might be due to the higher concentration of proliferation mediators such as EGF and PDGF and its higher content of vitamin A.

Attenuated salivary cortisol secretion under cue exposure is associated with early relapse.

AIMS: To test whether the risk of relapse in alcohol dependence is predicted by the subjective experience of cue exposure (CE) and/or cortisol reactivity to alcohol cues. METHODS: Salivary cortisol and self-ratings of 'tension' and 'desire to drink' were measured in 32 detoxified alcohol-dependent inpatients during CE sessions conducted in the first and third week of motivation enhancement therapy. Subjects completed the Toronto Alexithymia Scale (TAS-20) and the Abbreviated Alcohol Expectancy Questionnaire (B-AEQ) towards the end of the inpatient treatment to measure emotional self-awareness and the expected positive effects of alcohol. RESULTS: Six weeks after the end of the inpatient treatment, 15 patients were abstinent. Relapse was verified or was presumed for 17 patients. Those who had relapsed had shown an attenuated response to CE in the third week as an inpatient but did not differ from abstainers in terms of subjective reaction to cues. Subjective ratings of CE were not related to salivary cortisol or relapse but showed several associations with factors one and two of the TAS-20. The expectancy of enhanced social contacts by using alcohol (factor 1 of the B-AEQ) correlated negatively with the decline in salivary cortisol during the CE session in the third week of treatment. Subjective ratings of CE correlated with Alexithymiascores. CONCLUSIONS: Alcoholic patients who use alcohol to enhance their social contacts typically lack hypothalamo-hypophysical-pituitary-adrenocortical (HPA) reactivity in the early period of abstention. They are at an increased risk of early relapse and perhaps use alcohol to increase cortisol secretion again.

[Epitheliotrophic capacity of serum and plasma eyedrops. Influence of centrifugation]. / Epitheliotrophe Kapazität von Serum- und Plasmaaugentropfen. Einfluss der Zentrifugation.

BACKGROUND: Serum eyedrops are a new modality for the treatment of ocular surface disorders. We examined the influence of the preparation of blood products in a cell culture model and compared it with plasma. MATERIAL AND METHODS: Serum and plasma were obtained from full blood of ten healthy volunteers and centrifuged at 500 and 3000 G. EGF, PDGF, TGF-beta1, fibronectin, and vitamin A were quantified by means of ELISA and HPLC. Cultures of human corneal epithelial cells were incubated with the four blood products in dose-response experiments and the intracellular ATP quantified. RESULTS: EGF, PDGF, and vitamin A were present in serum in significantly higher concentrations than in plasma. The concentration of fibronectin was not influenced by the preparation. Support of proliferation was best by 25% platelet-poor serum. Serum supported the differentiation and migration of epithelial cells better than plasma. CONCLUSION: The biochemical character of serum eyedrops is determined by the parameters chosen to produce the blood product. Plasma does not seem to offer an epitheliotrophic capacity equivalent to serum eyedrops. Their production should be optimized before any meaningful randomized controlled clinical trial can be attempted.

Accuracy of point-of-care-testing (POCT) for determining hemoglobin concentrations.

BACKGROUND: While point-of-care testing (POCT) is being used increasingly as a basis for deciding on perioperative erythrocyte transfusion, no valid standards currently exist concerning the accuracy of Hb concentration measurements. For clinical employment, however, the confidence limits (+/-2 SD) of these measurements should lie close to 5 g/l. The aim of the present study was to evaluate the accuracy and precision of point-of-care testing for blood hemoglobin concentration (cHb in g/l) measurements in critically ill patients. METHODS: Fifty blood samples from 50 postoperative patients requiring intensive care treatment were withdrawn from a cannula in the radial artery into a 2-ml heparinized syringe (containing wet sodium heparinate in the conus), in a 2-ml Monovette with 50 IE lithium heparinate, and into a 2.7-ml cuvette with 1.6 mg potassium EDTA/ml blood. The POCT battery consisted of two blood gas analyzers (ABLTM 625 and 725, Radiometer, Copenhagen), the HemoCue system (Mallinckrodt Medical, Germany), and an automated hematology analyzer (M-2000(R), Sysmex, Germany). The cyanmethemoglobin method served as the reference 'gold standard' procedure. The blood gas analyzer and HemoCue systems were tested using dry and wet heparinized blood samples. RESULTS: Hemoglobin concentrations of the reference measurements ranged from 73.9 to 159.4 g/l. The automated hematology analyzer method did reveal a small but systematic deviation for higher cHb values. For the blood gas analyzer and HemoCue system procedures there was no systematic deviation of bias for either the first measurement or the averaged data. Bland & Altman analysis revealed a larger scattering for the wet heparinized samples. CONCLUSIONS: The above-stated requirement for POCT systems, i.e. that the confidence limits should lie close to 5 g/l cHb, held true for the dry heparinized samples of the blood gas analyzer (1st measurement and mean of 2), the HemoCue system (mean of 3) and the automated hematology analyzer.

Development and evaluation of a video program for presentation prior to elective cardiac surgery.

BACKGROUND: : The objective of the present study was to develop and evaluate the effects of a preparatory videotape on endocrine stress responses of patients prior to cardiac surgery and to analyze patient acceptance of this video for preoperative preparation. METHODS: : 101 male patients prior to elective cardiac surgery were enrolled into the study. On the day before surgery, patients were assigned to one of the following groups: group 1 (n = 51) saw a video with realistic information about the upcoming perioperative procedure, and group 2 (n = 50) saw a video of the same length without surgery-related information. Venous blood was sampled before and 15 min after the video presentation. On the second postoperative day, patients filled in a questionnaire concerning their experiences of having preoperatively watched the video. RESULTS: : After viewing the video, blood levels of cortisol, adrenocorticotropic hormone (ACTH), beta-endorphin, prolactin, epinephrine and norepinephrine in patients of group 1 were not significantly different compared to values measured before the video presentation. In patients of group 2, blood levels of cortisol, ACTH, prolactin and norepinephrine were significantly lower after video presentation compared to values obtained before the video. Patients of group 1 (compared to group 2) were significantly more often of the opinion that the video had helped in the preparation for surgery, and that they would like to repeat this adjunct preoperative video preparation in another similar situation. CONCLUSION: : We conclude from our results that (i); cardiac surgical patients prefer preoperatively an adjunct surgery-related video preparation to a non-specific video presentation, and that (ii); preoperative preparation with realistic information about the upcoming medical procedure in patients undergoing cardiac surgery does not lead to an increase in endocrine stress hormone levels.

Detecting and quantifying absorbed irrigation fluid by measuring mannitol and sorbitol concentrations in serum samples, and by ethanol monitoring.

OBJECTIVE: To describe a modified and improved technique which, in one measurement, estimates the influx of irrigation fluid during endoscopic endometrial ablation or prostate resection, and provides both rapid confirmation of the diagnosis and an estimate of the amount of fluid absorbed by detecting markers which pass from the irrigation fluid to the serum, i.e. mannitol or sorbitol. PATIENTS AND METHODS: Control samples were taken for analysis before irrigation, and test samples were taken on four occasions during and after intervention, from each of 10 patients undergoing transurethral resection of the prostate. Irrigation fluid was also marked with ethanol (1.5% w/v) and the concentration of this agent measured in the blood and expired air of these patients. The absorbed volume was calculated according to the extracellular distribution space of mannitol. RESULTS: Mannitol and sorbitol could be measured in 85% and 73% of the 40 test samples, respectively. The threshold for full sensitivity for breath ethanol concentration to detect absorption was 132 mL. CONCLUSION: This method for detecting serum mannitol and sorbitol represents a valid procedure for confirming and quantifying the absorption of irrigation fluid in the clinic, which agrees closely with the already established ethanol monitoring procedure and which should now be considered as a reference procedure.

Blood levels of atrial natriuretic peptide, endothelin, cortisol and ACTH in patients undergoing coronary artery bypass grafting surgery with cardiopulmonary bypass.

Previous studies demonstrated a biphasic time course with post-operative dissociation of blood levels of cortisol and ACTH in patients undergoing major surgery and critically ill patients. A possible role of endothelin and atrial natriuretic peptide (ANP) in the dissociation of concentrations of cortisol and ACTH in critically ill patients has been suggested. In the present study, we investigated the perioperative course of blood levels of endothelin, ANP, ACTH, and cortisol in 13 male patients undergoing cardiac surgery with cardiopulmonary bypass (CPB): group 1 consisted of 7 patients with an uneventful perioperative period and group 2 consisted of 6 patients with perioperative complications. Blood samples were taken pre-[T1], intra-[T2], post-operatively (on the day of surgery) [T3], as well as on the first [T4] and second [T5] post-operative days. Blood samples of endothelin, ANP, cortisol, and ACTH were measured using commercially available immunoassays. Perioperatively, a biphasic time course with post-operative dissociation of ACTH and cortisol concentrations was observed in all patients studied. Intraoperatively, during CPB, the highest levels of endothelin were found. Perioperatively, ANP and endothelin levels were elevated compared to pre-operative values up to the second post-operative day. On the second post-operative day, ANP concentrations were significantly higher in patients with complications in the perioperative period compared to those with an uneventful perioperative period. Our results suggest that: 1) plasma levels of ANP increased in patients with perioperative complications; 2) plasma levels of ANP may have prognostic value for patients undergoing cardiac surgery; and 3) the dissociation of ACTH and cortisol cannot solely be explained by the increase in endothelin-1 and ANP concentrations observed in patients undergoing major surgery.

Blood levels of corticosteroid-binding globulin, total cortisol and unbound cortisol in patients undergoing coronary artery bypass grafting surgery with cardiopulmonary bypass.

Previous studies have demonstrated a persistent rise in serum cortisol concentrations after cardiac surgery. To further investigate this finding and to evaluate the effect of hemodilution that occurs with the onset of cardiopulmonary bypass (CPB), concentrations of cortisol-binding globulin (CBG), total and unbound cortisol, and packed cell volume (PCV) were studied in 28 patients undergoing coronary artery bypass graft surgery. All patients received a standardized general anesthetic using a balanced technique with sufentanil, isoflurane, and midazolam. Blood was collected preoperatively, intraoperatively during CPB, and postoperatively in the evenings on the day of surgery and on the first and second postoperative day. Cortisol and CBG concentrations were measured by radioimmunoassay and were used to calculate the fraction of unbound cortisol. Serum CBG and cortisol concentrations corrected for hemodilution were significantly higher than non-corrected values. Perioperatively, CBG measurements were significantly intercorrelated. Intraoperatively, total and unbound cortisol concentrations were not significantly increased compared to preoperative values. Postoperatively up to the end of the study period serum concentrations of total and unbound cortisol were significantly increased compared to baseline values. Our results suggest that hemodilution occurs in all patients during cardiac surgery and continues up to the second postoperative day. This may lead to an underestimation of serum cortisol and CBG concentrations in patients undergoing heart surgery with CPB. Intraoperatively, concentrations of total and unbound cortisol were not significantly elevated. The postoperative rise in serum total cortisol concentration was accompanied by an increase in unbound cortisol concentration. The postoperative increase of unbound cortisol concentrations in patients undergoing cardiac surgery with CPB was largely due to an increase in cortisol secretion.

On-line analysis of electrolytes in extracorporeally circulating blood: application of a rat model to examine the effect of a single pharmacological dose of melatonin on electrolyte levels in blood.

An experimental model was developed to study the kinetics of electrolytes under different physiological and/or pathological conditions. The model was applied to investigate in vivo the effect of a pharmacological dose of melatonin on the concentrations of Ca2+, K+, Na+, and pH in the anticoagulated blood of anaesthetized male Wistar rats (250-350 g). After the application of 0.25 mg melatonin/kg body weight, injected intraperitoneally into each of 8 rats, the electrolytes were measured by a flow-through system with highly sensitive ion-selective electrodes. The results were compared to a control group (n=8) which was treated with diluent (saline). The electrolytes were monitored continuously via an extracorporeal circulation, on-going for at least 60 min. Melatonin induced a significant increase of blood Ca2+ (p<0.02) by an average of 9.9% after 60 min. However, total calcium concentration did not increase significantly. The extracorporeal circulation provoked an elevation of K+ by hemolysis. This K+ increase was slightly diminished by melatonin (p<0.06). No melatonin effects were seen on Na+, pH and magnesium in blood and plasma, respectively. Also, the urine concentrations of the electrolytes were not altered by melatonin. The mechanism by which melatonin influences the blood concentrations of ionized calcium and potassium is not yet understood.

The immune-endocrine interaction varies with the duration of the inflammatory process in cardiac surgery patients.

The present study investigated the perioperative course of cytokine release and hypothalamic-pituitary-adrenal (HPA) axis activation in relation to the duration of the inflammatory response in cardiac surgery patients. Twelve male patients scheduled for elective coronary artery bypass grafting surgery with cardiopulmonary bypass and general anaesthesia were divided into two study groups: group 1 (n=6) underwent surgery at 13.00 h+/-30 min, group 2 (n=6) at 08.30 h+/-50 min. Blood samples were collected preoperatively and up to the first postoperative day. Postoperatively, on the day of surgery, serum concentrations of the proinflammatory cytokines interleukin (IL)-6, IL-1beta and tumour necrosis factor (TNF)-alpha were not significantly different between the two groups, while blood concentrations of cortisol, adrenocorticotrophic hormone (ACTH) and beta-endorphin in group 2 patients were significantly higher than in group 1 patients. Postoperatively, on the day of surgery, ACTH and cortisol concentrations in group 1 patients were positively correlated to the blood concentrations of IL-1beta, IL-6 and TNF-alpha. By contrast, group 2 patients showed no significant relationship between cytokine release and activation of HPA axis at this time. Our results suggest that in patients undergoing cardiac surgery, the cytokine response is initiated before the HPA axis is fully activated. In the early postoperative period, cytokines appear to be involved in the activation of the HPA axis, while in the later postoperative period, high cortisol concentrations may inhibit the release of IL-6.

Is there an analytical or diagnostic advantage from including trisialo transferrin into the fraction of carbohydrate-deficient transferrin? Lessons from a comparison of two commercial turbidimetric immunoassays with the carbohydrate-deficient transferrin determination by high-performance liquid chromatography.

OBJECTIVES: Carbohydrate-deficient transferrin CDT has originally been defined as the sum of isotransferrins exhibiting isoelectric point values > or = 5.7 asialo, monosialo, and disialo transferrin but may also include at least in part trisialo transferrin when measured by modern commercial immunoassays. To examine the effects of divergently defining the analyte CDT, we compared two commercial assays yielding differently composed CDT fractions with a high-performance liquid chromatography HPLC assay commonly regarded as a reference method of CDT determination. METHODS: Relative CDT levels (CDT concentrations expressed as percent of total transferrin) were determined in 142 sera by (i) a turbidimetric immunoassay (ChronAlco I.D.) reportedly detecting asialo to disialo transferrin as CDT, (ii) an analogous assay (CDT Turbidimetric ImmunoAssay [TIA]) said to additionally include part of trisialo transferrin into the CDT fraction measured, and (iii) an anion-exchange HPLC method. Isotransferrins separated by the two commercial assays were also investigated by isoelectric focusing. RESULTS: Data from HPLC and isoelectric focusing indicate that the ChronAlco assay detects major parts of asialo, monosialo, and disialo transferrin as CDT while the CDT TIA yields CDT as the total of asialo, monosialo, disialo, and trisialo transferrin. When relative CDT concentrations obtained by both assays were classified as either normal or elevated according to reference ranges cited by the manufacturer and then were compared to analogously classified HPLC data, there were clearly more discrepancies between corresponding results from CDT TIA and HPLC (22%) than between ChronAlco and HPLC results (9%). CONCLUSION: Including trisialo transferrin into the CDT fraction enlarges the analytical signal and therefore slightly improves assay precision but also results in a significant number of pathologic results in samples exhibiting physiologic levels of the classical CDT components asialo to disialo transferrin. As long as the diagnostic information of the trisialo transferrin concentration is largely unknown, we strongly recommend not to include this isotransferrin into the determination of CDT.

Can one really measure magnesium deficiency using the short-term magnesium loading test?

OBJECTIVE: To compare a 1-h-version of a magnesium-loading-test (MLT) designed for outpatients in healthy controls with the 8-h standard; to establish the test in patients after renal transplantation prone to develop magnesium (Mg) deficiency; to correlate femur Mg-concentration and percentage retention of the given load. DESIGN: Comparison of mean values from healthy controls with respective from the literature; a prospective, randomized, controlled 4-month study; an intra-individual correlation of Mg-serum values and loading-test data with femur-Mg concentrations. SETTING: One centre study in a medical university; outpatients from the transplant unit; inpatients from the orthopedic unit. SUBJECTS: Twenty-four healthy controls aged 36.7 +/- 7.4 years; 34 patients after renal transplantation (46.5 +/- 14.3 years); 41 patients with hip replacement therapy (63.9 +/- 18.6 years). INTERVENTION: Baseline Mg values were measured by atomic absorption spectroscopy (AAS) in serum and urine. An intravenous Mg load with 0.1 mmol Mg-aspartate hydrochloride per kilogram bodyweight was given during 1 h. In 24 h-urine, the amount of excreted Mg was measured by AAS and the percentage retention of the given load calculated according to the formula: 1 - [Mg 24 h-urine/Mg test dose] x 100. Femur Mg was measured by AAS in a peace of the femur neck. Patients after renal transplantation were randomized after the first Mg load to either obtain daily 5 mmol Mg-aspartate hydrochloride per kilogram bodyweight, or placebo. Four months later a second loading-procedure was performed. MAIN OUTCOME MEASURE: Serum Mg, percentage retention of the given Mg load (%Ret) and femur Mg concentration. RESULTS: Mean serum Mg values were within the normal range. In controls, %Ret was -18 +/- 21 and not different from the literature. In the first MLT after renal transplantation, %Ret was 47 +/- 43. In patients under Mg medication it decreased significantly to 16 +/- 26, but was 58 +/- 27 in the placebo group. Femur Mg concentration was 62.6 +/- 20.9 mmol kg-1 dry substance and the corresponding %Ret was 14 +/- 28 with r = - 0.7093. CONCLUSION: The short-term version of the MLT is as good as the standard and was easily applied in outpatients. The indication from the good correlation between bone-Mg and %Ret and a marked decrease in %Ret in patients after Mg medication was that one can really measure magnesium deficiency.

Allopregnanolone in women with premenstrual syndrome.

5Alpha-reduced metabolites of progesterone, especially 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone) are now listed to neurosteroids. Their anesthetic properties can be explained by their allosteric interaction with GABA(A) receptors. A woman's organism is provided with an abundance of progesterone during the luteal phase of the menstrual cycle and its level falls down sharply with the first day of menses. The level of allopregnanolone follows that of progesterone. Many women suffer from so called premenstrual syndrome (PMS) during the luteal phase. In this study we have determined allopregnanolone and progesterone levels and their ratios in order to assess the over-all activity of C21-steroid 5alpha-reductase in these patients and in controls. Significantly lower levels of both progesterone and allopregnanolone than in controls have been found in PMS patients in the follicular phase only.

Persistent endocrine stress response in patients undergoing cardiac surgery.

To investigate the endocrine stress response in patients undergoing major surgery with general anesthesia using a balanced technique with sufentanil, isoflurane and midazolam up to the second postoperative day, blood levels of cortisol, epinephrine, norepinephrine, prolactin and growth hormone were determined in 68 males for elective coronary artery bypass grafting (CABG) surgery. Intraoperatively, during extracorporeal circulation none of the measured parameters were significantly increased compared to preoperative values. The endocrine response of patients with perioperative epinephrine medication (n = 32) was not significant different to patients that did not receive exogenous epinephrine (n = 36). On the evening of the day of surgery, levels of cortisol (3 fold), epinephrine (4.7 fold), norepinephrine (1.7 fold) and growth hormone (16.5 fold) were significantly increased. Compared to preoperative values levels of cortisol (3.3 fold), growth hormone (5.5 fold) and norepinephrine (1.8 fold) remained elevated up to the evening of the second postoperative day. In conclusion, the endocrine stress response in patients undergoing CABG-surgery under general anesthesia with sufentanil, midazolam, isoflurane is intraoperatively prevented by anesthesia. Although hemodilution or hormone degradation might be responsible for the lack of an increase in endocrine parameters during CPB, this study indicates that a balanced technique with isoflurane, sufentanil and midazolam is more effective in blocking the endocrine stress response than previously described anesthetic techniques. In the early postoperative period, a sharp increase in cortisol, epinephrine, norepinephrine and growth hormone occurred suggesting that the predominant endocrine stress response begins in the intensive care unit with end of anesthesia. The postoperative elevated levels of cortisol, growth hormone and norepinephrine indicate a persisting stress-response for more than two days after surgical trauma.