Reproducibility of three-dimensional ultrasound endometrial volume measurements in patients with postmenopausal bleeding.

OBJECTIVE: To evaluate the reproducibility of transvaginal three-dimensional (3D) endometrial volume measurement in patients with postmenopausal bleeding and to compare the reproducibility of this technique to that of two-dimensional (2D) endometrial thickness measurement. METHODS: In a prospective, blinded study, transvaginal ultrasound examinations were performed in 51 consecutive patients with postmenopausal bleeding. Three-dimensional volume and 2D thickness measurements were made and intraobserver and interobserver reproducibility of each technique were assessed. RESULTS: The intraobserver correlation of 3D endometrial volume measurement of the first observer was 0.97 and that of the second observer was 0.99. Thus, mean intraobserver correlation was 0.98. The mean interobserver correlation was 0.95 (0.95 vs. 0.96). There was no significant difference in reproducibility at different volume cut-offs. The mean intra- and interobserver correlation of endometrium volume measurements for five patients with endometrial carcinoma did not differ significantly from that for patients without carcinoma (0.98, 0.98 vs. 0.98, 0.95). The intraobserver correlation of 2D endometrial thickness measurements from the first observer was 0.71 and that from second observer 0.87. Thus, mean intraobserver correlation of the endometrial thickness measurements was 0.79. The mean interobserver correlation was 0.76 (0.84 vs. 0.70). CONCLUSIONS: Endometrial volume and thickness measurements by 3D and 2D ultrasound, respectively, show good reproducibility but the reproducibility of 3D ultrasound is better.

Embryo fragmentation in vitro and its impact on treatment and pregnancy outcome.

OBJECTIVE: To determine the impact of embryo fragmentation on pregnancy, obstetric, and perinatal outcome. DESIGN: Retrospective analysis of embryo transfers that were homogeneous in regard to the degree of fragmentation. SETTING: Fertility center. PATIENT(S): A cohort of 460 fresh embryo transfers. INTERVENTION(S): A total of 164 pregnancies were analyzed for the incidence of antepartum complications during gestation, obstetric (multiple pregnancy, preterm delivery, cesarean section), and perinatal outcome (sex, birth weight, admission to neonatal intensive care unit, malformations). MAIN OUTCOME MEASURE(S): Implantation and clinical pregnancy rate, obstetric and perinatal outcome. RESULT(S): Embryo fragmentation and number of embryos per transfer showed a significant influence on clinical pregnancy and implantation rate. No such relation was found concerning complications, multiple pregnancy rate, incidence of cesarean section, gestation week, birth weight, and average time at the neonatology. On the other hand, pregnancies derived from bad-quality embryos had a significantly higher rate of malformations. CONCLUSION(S): The higher percentage of malformations found in bad-quality embryos may be due to a higher percentage of apoptotic features and chromosomal disorders. For ethical reasons, the transfer of embryos with >50% fragmentation should be considered only after consultation with the patient.

Role of three-dimensional ultrasonographic measurement of endometrium volume as a predictor of pregnancy outcome in an IVF-ET program: a preliminary study.

OBJECTIVE: To evaluate the role of three-dimensional (3D) ultrasonographic measurement of the endometrium in predicting pregnancy in an IVF-ET program. DESIGN: Prospective study. SETTING: Center for assisted reproductive techniques. PATIENT(S): 65 women undergoing controlled ovarian hyperstimulation for IVF. INTERVENTION(S): Ultrasonographic examination on the day of hCG administration. MAIN OUTCOME MEASURE(S): Endometrial volume, endometrial thickness, and pregnancy rate. RESULT(S): The mean (+/-SD) endometrium volume (4.16 +/- 1.97 mL), endometrium thickness (11 +/- 2 mm), and estradiol level (1686.82 +/- 1057.10 pg/mL) in 21 pregnant women on the day of hCG administration did not differ statistically differ from the respective values in 44 nonpregnant women (4.53 +/- 1.79 mL; 11 +/- 2 mm, 1883.56 +/- 1147.21 pg/mL). Receiver-operating characteristic curves showed that the area under curve (AUC) was 0.57 for endometrial volume and 0.48 for endometrial thickness. Using a cut-off value of 2.5 mL for endometrial volume to predict pregnancy, results of the Fisher exact test were statistically significant. No significant cut-off value was found for endometrial thickness. CONCLUSION(S): Endometrial volume and thickness on the day of hCG administration did not predict occurrence of pregnancy. A minimum volume of 2.5 mL appeared to favor pregnancy. The predictive value of 3D ultrasonographic measurement of endometrial volume and thickness was better than that of 2D measurement.

Three-dimensional endometrial volume estimation as a predictor of pituitary down-regulation in an IVF-embryo transfer programme.

To examine the role of three-dimensional (3D) volume estimation in predicting pituitary down-regulation in an IVF-embryo transfer programme, 46 women were treated with buserelin acetate for down-regulation prior to and concomitantly with ovarian stimulation. Receiver operating characteristic (ROC) curve analysis was used for statistics. The area under the curve (AUC) provides a measure to show how good (AUC close to 1) or how poor (AUC close to 0.5) a test is. If down-regulation was defined as oestradiol <40, <60 or <80 pg/ml, the AUC of 3D-ultrasound was 0.57, 0.83 and 0.97 respectively. The highest sensitivity (100%) and specificity (93.2%) of 3D-ultrasound was achieved if down-regulation was defined as oestradiol <80 pg/ml (n = 44), with an endometrial volume of 1.9 ml. If down-regulation was defined as oestradiol <60 pg/ml (n = 42) the best combination of highest sensitivity (95.2%) and specificity (75. 0%) was obtained with an endometrial volume of 1.9 ml. The comparison of 3D volume calculation with endometrial thickness measurement revealed no significant difference in predicting down-regulation. 3D volume estimation provides a new tool for diagnosing relative hypo-oestrogenism or down-regulation, but it was not superior to two-dimensional ultrasound.

Intestinal elimination of hydroxyethyl starch?

OBJECTIVE: Hydroxyethyl starch (HES) is mainly eliminated via the kidneys. Any information about extrarenal elimination obtained so far has been either incomplete or contradictory. The objective of this study was to quantify the intestinal excretion of infused HES with a mean molecular weight of 200,000 and a molar substitution of 0.5 (HES 200/0.5) and to compare the reappearance/recovery rate in urine and plasma. DESIGN: Prospective clinical study without control group. SETTING: The study was conducted at the Institute of Hypertension of the Society of Clinical Pharmacology, Vienna, Austria, which is an establishment for research in volunteers. PARTICIPANTS: The results of six out of seven healthy male volunteers were appropriate for analysis. One trial subject had to be excluded from the study because of severe protocol violation (mixing of stool and urine samples). INTERVENTIONS AND METHODS: Each volunteer was administered 500 ml of 10% HES 200/0.5 in a 0.9% NaCl solution intravenously within 1 h. A gut lavage with 6 l of a polysaccharide free solution was continuously administered from 3 h prior to until 2 h after the HES infusion to facilitate the collection of the samples and to exclude any source of error at analysis. HES was quantified with the hexokinase method. MEASUREMENTS AND RESULTS: Right from the beginning of the infusion until 10 h after its completion, the cumulative HES excretion with feces (principle parameter) and urine as well as selective plasma volume and HES plasma level were measured. Six and 14 h after the infusion had been completed, the recovery rates of HES in urine were about 30% and 40%, respectively, and in plasma about 23% and 8%, respectively. By contrast, not more than a kind of "background noise amount" of HES (about 0.2 %) could be recovered in feces ( mean value in % of the infused amount of the substance). Six and 14 h after the infusion had been completed, the total recovery rates of HES were 53% and 49%, respectively. CONCLUSION: In a physiologically unimpaired gut HES 200/0.5 is not, or only to an infinitesimal extent, eliminated via the intestine. The question if there is any alternative path to renal excretion for HES still remains to be answered. As the calculated reappearance/recovery rate of HES is only about 50 % of the administered dose, further investigations as to the final fate of HES appear necessary.

Haemodynamic changes during thoracoscopic surgery the effects of one-lung ventilation compared with carbon dioxide insufflation.

We investigated the haemodynamic and respiratory effects of one-lung ventilation and carbon dioxide insufflation in 13 adult patients undergoing video-assisted thoracoscopy. Cardiorespiratory variables were determined during carbon dioxide insufflation at intrahemithoracic pressures of 5, 10 and 15 mmHg, and after 5 and 15 min of one-lung ventilation. Carbon dioxide insufflation was associated with a clear deterioration in circulatory function. The cardiac index decreased subsequent to increasing intrathoracic pressures. The mean cardiac index (SD) at pressures of 10 and 15 mmHg was 1.86 (0.39) and 1.52 (0.46), respectively, and may be compared with the reduced venous return consistent with tension pneumothorax. One-lung ventilation did not affect haemodynamic variables but reduced arterial oxygenation indices (PaO2/FIO2) from 424.29 (160.79) after induction of anaesthesia, to 207.72 (125.50) after 5 min and 172.04 (72.03) after 15 min of one-lung ventilation, respectively. The oxygenation index was not influenced by intrahemithoracic carbon dioxide insufflation. One-lung ventilation via a double-lumen endobronchial tube is safe and convenient for video-assisted thoracoscopic surgery. It has no further consequences on haemodynamic variables, whereas the compression of the lung by carbon dioxide insufflation may cause circulatory dysfunction.

Reproducibility of transvaginal three-dimensional endometrial volume measurements during ovarian stimulation.

Before estimating the clinical role of a method, the reproducibility has to be evaluated precisely. This study aimed to document the reproducibility of the endometrial volume measurement by three-dimensional (3D)-ultrasound. The volume measurements were done on 57 consecutive in-vitro fertilization (IVF) patients with either the full planar (contour) or the three distance method. A paired t-test provided no statistically significant difference between the two methods. Linear regression analysis, using the full planar method as independent and the other as dependent variables, yielded the following results: intercept = 0.348, not statistically different from 0; slope = 0.962, statistically different from 1 (P < 0.01). Interobserver reliability for the three distance method was 0.6667 and for the full planar method was 0.9565. Intra-observer reliability for the three distance method was 0.8426 and for the full planar method 0.9394. The correspondence between and within observers seemed to be good. Both methods are reliable, but the full planar method seems to provide slightly better reproducibility in regard to endometrium volume measurement.

Hydroxyethyl starch antibodies in humans: incidence and clinical relevance.

UNLABELLED: Hydroxyethyl starch (HES) is a plasma expander used for perioperative i.v. fluid management, as well as for resuscitation from trauma and shock. HES is very well tolerated, and the incidence of anaphylactic reactions is lower than with dextran or gelatin. Dextran anaphylaxis is caused by circulating dextran-reactive antibodies (ABs) of the immunoglobin G (IgG) class found in most adults. Histamine release from mast cells induces adverse reactions after gelatin infusion. The cause of adverse reactions due to HES is not yet clear. To investigate AB formation due to HES, we collected sera of 1004 patients at least 14 days after starch administration. Using a highly sensitive enzyme-linked immunoabsorbent assay technique, we found one patient with a low 1:10 titer of HES-reactive ABs (immunoglobin M [IgM] class). Despite repeated HES infusions, no clinical reaction could be detected in this patient. On the basis of a binomial distribution, a one-tailed confidence interval (99%) was used to calculate the percentage of the occurrence of ABs in general with maximum of 33 in 10,000 persons (IgM) and 23 in 10,000 persons (IgG). We suggest that HES-reactive ABs are extremely rare and that they do not necessarily induce anaphylaxis. Other mechanisms may be responsible for adverse reactions due to HES. IMPLICATIONS: The frequency of antibody formation due to hydroxyethyl starch, a commonly used plasma expander, was prospectively investigated in 1004 patients. Only one patient showed transient antibody formation, which was not harmful to the patient. This low antigenicity could explain the excellent tolerance of hydroxyethyl starch compared with other plasma expanders.

Hypervolemic hemodilution in acute ischemic stroke: the Multicenter Austrian Hemodilution Stroke Trial (MAHST).

BACKGROUND AND PURPOSE: Experimental studies suggest a beneficial effect of hemodilution on acute ischemic stroke. This was not proven by previous multicenter trials in the clinical setting. Various reasons have been suggested for the failure of these studies, which we attempted to consider in the Multicenter Austrian Hemodilution Stroke Trial (MAHST). METHODS: MAHST is a randomized, double-blind, placebo-controlled study of hypervolemic hemodilution (HHD) within 6 hours of a clinically first ischemic stroke localized in the middle cerebral artery territory. The treatment consisted of 10% hydroxyethyl starch 200/0.5 (HES) and was tested against pure rehydration with Ringer's lactate over a period of 5 days. Our primary outcome measure was clinical improvement within 7 days as measured by the Graded Neurologic Scale (GNS). We performed an adaptive interim analysis to reevaluate the study goal after entering half of the projected number of patients (n = 200). At least 600 patients per group would have been required for significant results, and therefore we decided to terminate the trial. RESULTS: Ninety-eight patients received HHD and 102 patients placebo. The baseline characteristics were comparable between both groups. In the HHD group the absolute reduction of the hematocrit was 2.5% on day 2 with a maximum of 3.7% on day 5, which compares with a reduction in the placebo group of 1% and 1.9%, respectively. Intention-to-treat analysis showed no significant difference of the change of the GNS scores between HHD-treated (median, -8.5; 95% confidence interval, -14.2 to -4.0) and placebo-treated patients (median, -6.0; 95% confidence interval, -11.0 to 0.0) on day 7, and GNS scores remained similar in both treatment groups throughout the trial. At 3 months, slightly more HHD patients showed complete independence on the Barthel Index (28 versus 24), and fewer HHD than placebo patients had died (13 versus 17), but these differences were not statistically significant. HHD treatment was not associated with any specific adverse event. CONCLUSIONS: Mild HHD is safe but failed to demonstrate a significant beneficial effect over the pure rehydration regimen in patients with acute ischemic stroke.

Influence of a novel amino acid solution (enriched with the dipeptide glycyl-tyrosine) on plasma amino acid concentration of patients with acute renal failure.

In this randomized, double-blind controlled study we compared the effect of parenteralnutrition with two different amino acid solutions on the plasma concentration of amino acids in 27 patients with acute renal failure. Fourteen patients received the new dipeptide-containing (glycyl-tyrosine) amino acid solution (AADI) in combination with glucose (60%) and fat (10%) as an 'all-in-one' solution over 120 h continuously via a central venous catheter. In the control group (AAST), parenteral nutrition with a standard amino acid solution in isonitrogenous and isocaloric form (0.7 g amino acids/kg BW/day and 25 kcal/kg BW/day) was administered to 13 patients over the same period of time. The administration of the dipeptide-containing amino acid solution caused a return to within the normal range of most of the amino acid concentrations which were decreased at the onset. A significant difference could be found between the AADI and AAST group for the achieved plasma concentrations of threonine (P < 0.01), phenylalanine (P<0.05), isoleucine (P<0.05), tryptophan (P<0.01) and ornithine (P<0.05), The phenylalanine/tyrosine ratio, did not change in the AADI group, while a marked increase was observed in the AAST group. (152.7 +/- 23.5 - 159.8 +/- 37.6 vs 172.6 +/- 24.6 - 310.6 +/- 136.7, respectively). The plasma concentration of glycyl-tyrosine was at the limit of detectability indicating rapid hydrolysis of the dipeptide in acute renal failure. These data suggest that the new dipeptide-containing amino acid solution offers a clear advantage over a standard amino acid formulation in correcting the amino acid imbalances in plasma of patients with ARF and is able to maintain normal tyrosine concentrations and phenylalanine/tyrosine ratio.

[Comparison of postoperative volume therapy in heart surgery patients]. / Vergleichende Untersuchungen zur postoperativen Volumentherapie bei kardiochirurgischen Patienten.

UNLABELLED: Patients who have undergone cardiac surgery with use of extracorporeal circulation frequently reveal marked hypovolaemia in spite of a highly positive fluid balance. This is thought to be due to transient microvascular damage and extravascular fluid shift. Further volume replacement to achieve haemodynamic stability in the postoperative period may cause fluid overload and congestive heart failure. The present study was designed to investigate whether this fluid overload could be avoided by using a hypertonic-hyperoncotic solution (group I: HHL, 10% hydroxyethylstarch 200/0.5 in 7.2% saline) instead of two different standard colloid solutions (group II: HA, 5% albumin; group III: HES, 6% hydroxyethylstarch in 0.9% saline). METHODS: Twenty-one patients meeting our criteria for hypovolaemia immediately after cardiac surgery were randomly assigned to three groups. Patients in group I received HHL in increments of 150 ml, while patients in group II and group III were given HA and HES respectively in increments of 500 ml until hypovolemia was corrected. Haemodynamic assessment was done using a pulmonary artery thermodilution catheter. Intra- and extravascular volumes, including extravascular lung water (EVLW), intrathoracic blood volume (ITBV), and total blood volume (TBV) were measured by the double indicator technique using lung water software (COLD-System, Pulsion, Munich, Germany). RESULTS: Correction of hypovolaemia-related haemodynamic parameters and restoration of normal TBV were achieved by 236 +/- 80 ml of HHL (group I), 857 +/- 244 ml of HA (group II) and 1000 +/- 0 ml of HES (group III) respectively. TBV increased significantly in each group, compared to baseline values. EVLW did not change significantly in any group. We found that the volume-augmenting effect of HHL per millilitre infused solution was more than four times that of HA and HES, primarily as a result of increasing plasma osmolality due to an increase of plasma sodium levels. This pronounced effect on intravascular volume of HHL lasted for only 2 h following infusion, however, and did not lead to any unwanted side effects. In the period between 2 and 20 h after primary volume replacement, further fluid therapy with colloids and crystalloids, guided by clinical signs of hypovolaemia, was necessary in each group of patients. The overall fluid requirements for the first 20 h after operation did not differ among the three resuscitation regimens. CONCLUSION: We found that HHL is a safe and effective solution for acute correction of hypovolaemia after cardiac surgery. The advantages of a smaller initial volume load by HHL cannot be maintained for longer than 2 h.

[Degree of substitution and volume expanding effect of various medium molecular weight hydroxyethyl starch solutions]. / Substitutionsgrad und volumenexpandierender Effekt unterschiedlicher mittelmolekularer Hydroxyäthylstärke (HAES)-Lösungen.

Hydroxyethylstarch (HES) is today one of the most frequently used artificial plasma substitutes in prehospital, as well as in clinical settings. However, there are no studies comparing the volume effect of different HES solutions. The goals of the present study therefore were to compare the volume effect of three HES solutions, which are similar with regard to mean molecular weight but different in concentration and degree of substitution. The obtained results enable guidelines for fluid resuscitation in hypovolemia to be laid down. In 30 patients fulfilling the ASA physical status classification I and II 500 ml of either 10% HES 200/0.5, 6% HES 200/0.5 or 6% HES 200/0.6-0.66 were infused within 30 min. The effect of each solution was evaluated using the mechanical oscillator technique (MOT). This technique measures precisely density changes of blood and plasma and allows-using standard formulae-calculation of blood and plasma volume changes. All 3 HES solutions showed similar effects in increasing plasma volume. Immediately after the end of infusion plasma volume was increased by about 800 ml with 10% HES and by about 650 ml with 6% HES 200/0.5. The volume expanding effect of 6% HES 200/0.6-0.66 amounted to 700 ml. The volume expanding effect of all starches decreased only slightly during the following two hours; an interesting detail observed was a second volume effect of HES (about 20% of the volume infused). We conclude that for the correlation of fluid deficits due to trauma, hemorrhage and shock HES solutions seem to be most effective artificial plasma substitutes.(ABSTRACT TRUNCATED AT 250 WORDS)

["Small volume resuscitation"--does it open new possibilities in the treatment of hypovolemic shock?]. / "Small volume resuscitation"--Eröffnen sich damit neue Möglichkeiten in der Behandlung des hypovolämischen Schocks?

Hypertonic-hyperoncotic solutions are a supplementation to conventional fluid regimens in the management of hypovolemia due to trauma, hemorrhage and shock. In this review the possible modes of action of these solutions are discussed and their efficacy both in experimental and clinical settings is presented. Possible side effects, such as hypernatremia and possible problems in the presence of increased intracranial pressure, following administration of hypertonic-hyperoncotic solutions are discussed, as well as the reaction of normovolemic patients to such infusions.