Alterations in bile acid synthesis in carriers of hepatocyte nuclear factor 1α mutations.

OBJECTIVES: Heterozygous mutations in hepatocyte nuclear factor 1α (HNF1α) cause maturity onset diabetes of the young 3 (MODY3), an autosomal dominant form of diabetes. Deficiency of HNF1α in mice results in diabetes, hypercholesterolaemia and increased bile acid (BA) and cholesterol synthesis. Little is known about alterations in lipid metabolism in patients with MODY3. The aim of this study was to investigate whether patients with MODY3 have altered cholesterol and BA synthesis and intestinal cholesterol absorption. A secondary aim was to investigate the effects of HNF1α mutations on the transcriptional regulation of BA metabolism. METHODS: Plasma biomarkers of BA and cholesterol synthesis and intestinal cholesterol absorption were measured in patients with MODY3 (n = 19) and in matched healthy control subjects (n = 15). Cotransfection experiments were performed with several promoters involved in BA metabolism along with expression vectors carrying the mutations found in these patients. RESULTS: Plasma analysis showed higher levels of BA synthesis in patients with MODY3. No differences were observed in cholesterol synthesis or intestinal cholesterol absorption. Cotransfection experiments showed that one of the mutations (P379A) increased the induction of the cholesterol 7α-hydroxylase promoter compared with HNF1α, without further differences in other studied promoters. By contrast, the other four mutations (L107I, T260M, P291fsinsC and R131Q) reduced the induction of the farnesoid X receptor (FXR) promoter, which was followed by reduced repression of the small heterodimer partner promoter. In addition, these mutations also reduced the induction of the apical sodium-dependent bile salt transporter promoter. CONCLUSIONS: BA synthesis is increased in patients with MODY3 compared with control subjects. Mutations in HNF1α affect promoters involved in BA metabolism.

Abnormal antenatal Doppler velocimetry and cognitive outcome in very-low-birth-weight infants at 2 years of age.

OBJECTIVE: To study neurodevelopmental outcome at 2 years of corrected age in very-low-birth-weight (VLBW) (< or = 1500 g) preterm infants with abnormal fetoplacental flow. METHODS: A total of 258 VLBW infants were born at Turku University Hospital between 2001 and 2006. Of these, 99 had undergone, within 1 week of delivery, antenatal Doppler assessment of blood flow in the umbilical artery (UA), fetal middle cerebral artery (MCA), descending aorta (DAo), aortic isthmus and ductus venosus and were eligible for inclusion in the study. Postnatally brain pathology was assessed by serial ultrasound and magnetic resonance imaging in 86 of the neonates and brain volume was measured in 80. Cognitive development was evaluated at 2 years of corrected age in 83 infants using the Bayley Scales of Infant Development-II. Motor development was assessed using the Hammersmith Infant Neurological Examination. RESULTS: On univariate analysis, abnormal pulsatility index (PI) in the UA and an abnormal UA-PI/MCA-PI ratio (P = 0.04 and P = 0.003, respectively) as well as increases in both the DAo-PI and in the DAo-PI/MCA-PI ratio (P = 0.03 and P = 0.02, respectively), were associated with adverse cognitive outcome at 2 years of age. However, when controlling for cerebral volume using multivariate analysis, the association between abnormal antenatal Doppler characteristics and cognitive outcome became statistically non-significant, which indicated the determinant role of the volume reduction. Motor development was not associated with antenatal Doppler indices. CONCLUSION: Abnormal antenatal Doppler indices are associated with adverse cognitive outcome at 2 years in VLBW infants. Our findings suggest that this association may be mediated through brain volume.

Infants born to women with substance use: Exploring early neurobehavior with the Dubowitz neurological examination.

BACKGROUND: There is a special concern regarding substance using pregnant women due to the possible adverse effects on the infant. While the immediate effects of prenatal substance exposure are well known, the long-term data on the infants' neurodevelopment is inconclusive. AIMS: The purpose of this study was to assess early neurobehavior of infants of mothers with substance use using the Dubowitz examination and to follow their neuromotor development until one year of age. STUDY DESIGN AND SUBJECTS: Ninety-five pregnant women with a recent history of substance use were recruited and followed up at the maternity outpatient clinic. Follow-up data was collected from hospital records and maternal interviews. The Dubowitz neurological examination was performed to the 54 clinically healthy term infants. The results were converted into optimality scores and compared to normative values from clinically healthy term infants derived from a separate normative population. The infant's neuromotor development was followed up to one year of age. RESULTS: Only 7% of the infants born to women with recent or current substance use reached optimal scores (<30.5) in the Dubowitz neurological examination compared to 95% reported in normative population. Sixty-three percent of the newborns needed follow-up based on physiotherapeutic assessment of neurobehavior. By 12 months of age, the neuromotor status of 88% (n = 30) of these infants was found normal. CONCLUSIONS: A high percentage of infants of mothers who were referred prenatally to hospital due to substance use showed suboptimal neurological findings during their first days of life.

Change in heart rate variability in relation to a significant ST-event associates with newborn metabolic acidosis.

OBJECTIVE: To find whether low-to-high frequency (LF/HF) ratio of fetal heart rate (FHR) variability changes in relation to a significant ST-event during delivery, and if the change is predictive of metabolic acidosis of the newborn. DESIGN: A case-control study. SETTING: Data from a multicentre project. SUBJECTS: Acidotic and control fetuses with abnormal cardiotocography together with a ST-event in fetal electrocardiogram (ECG). METHODS: We studied intrapartum FHR variability with spectral analysis from 34 fetuses with a significant ST-event in the fetal ECG. LF/HF ratio of FHR variability was measured within a period of 1 hour before and 1 hour after a significant ST-event. Sensitivity and specificity of the change in LF/HF ratio of FHR variability in prediction of metabolic acidosis (pH < or = 7.05 and base deficit value > 12.0 mmol/l) of the newborn were described by means of the receiver operating characteristic curve. MAIN OUTCOME MEASURES: Change in LF/HF ratio of FHR in relation to a significant ST-event. RESULTS: We found that a relative change in LF/HF ratio greater than 30% in relation to a significant ST-event predicted cord arterial metabolic acidosis with a sensitivity of 89% (95% CI 68-100%) and specificity of 80% (95% CI 64-96%). CONCLUSIONS: Relative changes in LF/HF ratio of FHR variability in relation to a significant ST-event are more pronounced in fetuses born with metabolic acidosis.

Effect of the 3'-untranslated region on the expression levels and mRNA stability of alpha 1(I) collagen gene.

Changes in the synthesis of type I collagen, a major extracellular matrix component in skin and bones, are associated with both normal growth or repair processes and with several pathological conditions such as lung fibrosis and liver cirrhosis. The expression of the alpha 1(I) collagen gene is regulated by transcriptional and post-transcriptional mechanisms. Regulation at both these levels are usually utilised when extensive changes occur in collagen synthesis. We constructed plasmids carrying the whole or partially deleted 3'-UTR sequences of the alpha 1(I) collagen gene, fused to two hGH exons and to the promoter of the alpha 1(I) collagen gene. A control plasmid contained the 3'-UTR of the hGH gene. In transient transfections into Rat-1 fibroblasts, no significant differences between plasmids were found, which suggests that although 3'-end of the gene has been shown in previous studies to contain DNaseI hypersensitive sites and to bind sequence-specific nuclear proteins it does not seem to function as a transcriptional regulator. This was further supported by the finding that TGF-beta treatment induced a 2.5-fold expression of hGH mRNA from plasmids containing collagen promoter and either hGH or alpha 1(I) collagen 3'-UTR. In stable transfections, mRNAs using the first polyadenylation site were not as stable as those transcribed from the endogenous alpha 1(I) collagen gene. We suggest that the 3'-UTR alone may not be sufficient to determine the stability of the shorter alpha 1(I) collagen mRNA species.

Docetaxel: standard recommended dose of 100 mg/m(2) is effective but not feasible for some metastatic breast cancer patients heavily pretreated with chemotherapy-A phase II single-center study.

PURPOSE: Patients with metastatic breast cancer, especially those with progression after several prior chemotherapy treatments, need efficient chemotherapy. This study investigates the efficacy and toxicity of docetaxel in metastatic breast cancer patients with previous chemotherapy for metastatic disease. PATIENTS AND METHODS: Thirty-one women (median age, 52 years; range, 40 to 65 years) treated for metastatic breast cancer with docetaxel were included. Eleven patients had one metastatic site, 10 patients had two, and 10 patients had three or more. The planned dose of docetaxel per course was the standard treatment of 100 mg/m(2) (or 75 mg/m(2) if liver enzyme levels were abnormal) every 3 weeks, given for six or eight cycles. RESULTS: The overall response rate was 48% (three complete responses [CR] and 11 partial responses [PR] ), and the median duration of response was 7 months (range, 2 to 16 months). Twenty patients (65%) experienced fatigue, and 27 patients (87%) had alopecia. Fifteen cases (48%) of grade 4 leukopenia were observed. Edema with a weight gain of 2 to 15 kg was seen in 12 patients (39%), and mucositis occurred in 20 patients (65%). Twenty-three patients (74%) interrupted treatment before reaching the planned number of courses, nine patients owing to progression of cancer and 14 owing to toxicity. Dose reduction was required in 18 (61%) of the patients. Only two patients were able to receive the planned eight courses without dose reduction. CONCLUSION: Docetaxel is highly active in metastatic breast cancer, even as a third-line treatment, and can be considered as an efficient standard option in second-line treatment. The standard recommended dose level of 100 mg/m(2) is not feasible in heavily pretreated patients; therefore, for such patients, an initial dose level not exceeding 75 mg/m(2) is recommended.

Expression of extracellular matrix genes: transforming growth factor (TGF)-beta1 and ras in tibial fracture healing of lathyritic rats.

Experimental osteolathyrism, induced by dietary aminoacetonitrile (AAN), was used to study the effect of altered extracellular matrix on the expression of connective tissue components in long bone healing. AAN inhibits lysyl oxidase, which is needed for the formation of collagen cross-link precursors, and is also shown to act as a regulator of Ras. Fractured tibias in lathyritic rats develop excessive amounts of mechanically weak callus tissue with irregular cartilage and reduced glycosaminoglycan accumulation. Cartilage-specific proteins (collagen types II, IX, and X and aggrecan) were expressed temporally much wider in lathyritic calluses than in the controls, and active transcription was observed even during the fibrous and ossifying stages. Soft connective tissue was still present in 2- and 3-week-old lathyritic calluses and could explain the elevated type III collagen, biglycan, and decorin mRNA levels. Both transforming growth factor (TGF)-beta1 and c-Ha-ras, which control cell growth and differentiation, were upregulated during the cartilaginous stage. The maximal expression of TGF-beta1 preceded that of ras in osteolathyrism.

Paclitaxel changes sympathetic control of blood pressure.

Paclitaxel has become part of standard therapy in the treatment of ovarian and breast cancer. Concern has been raised about the effects of paclitaxel on cardiovascular function. Therefore, this study of the effects of paclitaxel on autonomic cardiovascular control was initiated. Eighteen women treated for ovarian or breast cancer were examined with autonomic cardiovascular function tests, once before the treatment and once after the second course of paclitaxel. Heart rate and blood pressure variability and changes in heart rate and blood pressure responses to the tests were measured. Baroreflex sensitivity was calculated from the Valsalva manoeuvre non-invasively. Paclitaxel did not change heart rate variability at rest compared with the pretreatment level. However, medium frequency variability of blood pressure was smaller after treatment with paclitaxel. Paclitaxel treatment did not impair the heart rate and blood pressure responses to the autonomic function tests. The results do imply that paclitaxel alters sympathetic control of blood pressure. Nevertheless, paclitaxel does not appear to precipitate autonomic cardiac neuropathy.

Pre-eclampsia does not change the adhesion molecule status in the placental bed.

During normal placentation trophoblast cells invade maternal tissues and remodel the uterine arteries into low-resistance channels. In pre-eclampsia, trophoblast invasion is impaired and this, along with endothelial dysfunction, has been suggested to play a role in the pathogenesis of pre-eclampsia. We studied the expression of adhesion molecules important for leukocyte extravasation in the placental bed with immunohistochemistry and compared the expression in pre-eclampsia to that in normal pregnancy. Our major finding was that only invasive trophoblasts expressed cutaneous lymphocyte antigen-1 (CLA-1) in the third trimester of pregnancy, whereas villous trophoblasts did not. In the first trimester both villous trophoblasts and invasive trophoblast cells in decidua remained negative for CLA-1. Pre-eclampsia did not change the expression of leukocyte-endothelium adhesion or lymphocyte homing-associated antigens, ICAM-1, ICAM-2, VCAM, P-selectin, E-selectin, L-selectin, CLA-1, CD73, VAP-1 and alphaEbeta7 in the placental bed. Furthermore, pre-eclampsia was not associated with an aberrant accumulation of lymphocytes carrying antigens of any particular known organ-specific homing systems. The results on the unchanged pattern of adhesion molecule expression in pre-eclampsia suggests that there is no major change in the adhesive properties of the endothelium of the placental bed in pre-eclampsia.

Expression of syndecan-1 in human placenta and decidua.

Syndecan-1 is a cell surface heparan sulphate proteoglycan, which binds to the extracellular matrix (ECM), growth factors and antithrombin III. The early expression of syndecan-1 during mouse embryonic development suggests a potential role in the communication between the embryo and the ECM of decidua. Using immunohistochemical methods, the present study showed that the expression of syndecan-1 in the trophoblast cells changes along trophoblast differentiation. The syncytiotrophoblasts in the chorionic villi exhibited an apical expression of syndecan-1. This suggests that the expression is restricted to non-migrating, non-proliferating trophoblasts. The mode of syndecan-1 expression by human placental trophoblasts is independent of gestational age. The expression is not changed in miscarriages. In pre-eclampsia, the staining for syndecan-1 on the villous syncytiotrophoblast is weaker compared to normal pregnancy, but in placental bed the expression is similar. The unique apical localization of syndecan-1 in chorionic villi, not detected in any other tissues, suggests a potential role in fetomaternal communication probably via growth factor binding and in anticoagulation of intervillous circulation.

Immediate effects of docetaxel alone or in combination with epirubicin on cardiac function in advanced breast cancer.

The immediate effects on cardiac function of 3-weekly docetaxel and combined docetaxel-epirubicin were evaluated during treatment of metastatic breast cancer using assessment of heart rate variability (HVR) and left ventricular ejection fraction (LVEF) measured by echocardiography. Twenty-four breast cancer patients were treated with docetaxel alone (starting dose 100 mg/m2) and 34 with a combination of docetaxel and epirubicin (starting dose for both drugs 75 mg/m2) administered 3-weekly. Single docetaxel caused no significant changes in HVR or cardiac function, whereas during combined treatment statistically significant changes were observed in mean RR intervals and in the number of supraventricular extrasystoles. Clinically the observed changes were insignificant. In conclusion, in 3-weekly administration the combined use of docetaxel and epirubicin was more likely than single docetaxel to cause changes in cardiac function.

Docetaxel, a promising novel chemotherapeutic agent in advanced breast cancer.

UNLABELLED: Clinical practice in chemotherapy of breast cancer is undergoing changes. This study investigated the efficacy and toxicity of docetaxel, a novel chemotherapeutic agent in metastatic breast cancer. Focus was on the effect of the cumulative dose of previous anthracycline treatment on response rate, toxicity and survival in our own patients; published data were reviewed. PATIENTS AND METHODS: Thirty-one women, (median age 52 years, range 40-65) treated for metastatic breast cancer with docetaxel were included. RESULTS: The overall response rate was 48%, with 3 complete and 11 partial responses (95% CI 29-66). The duration of response was 7 months (range 2 to 16 months), the median overall survival after docetaxel 13.7 months for responding patients, 14.3 months in no-change patients and 6.5 months in patients with progressive disease. The mean cumulative anthracycline dose prior to docetaxel was 860 mg (range 200-1760 mg); in the case of responders, the previous cumulative total epirubicin doses were 200-1575 mg (median 766 mg.). Total dose or schedule of previous epirubicin treatment had no impact on docetaxel response rate, toxicity or survival. The response seen in this study is within the published range (24 to 60%) observed for docetaxel in anthracycline-treated patients. CONCLUSION: We conclude that docetaxel is active in metastatic breast cancer even as third- line treatment. Previous treatment with, or response to, epirubicin does not influence the response to docetaxel and this promising new drug is currently being tested for adjuvant use in breast cancer.

Docetaxel and autonomic cardiovascular control in anthracycline treated breast cancer patients.

BACKGROUND: Taxoids are new chemotherapeutic agents effective in the treatment of breast cancer. Paclitaxel treatment has been reported to cause some cardiac side effects and both paclitaxel and docetaxel to cause mild, mainly sensory, peripheral neuropathy. Autonomic function tests are sensitive measures of autonomic neuropathy and cardiac regulation. The purpose of this study was to find out whether docetaxel changes neural cardiovascular regulation in breast cancer patients previously treated with anthracyclines. PATIENTS AND METHODS: Nine women treated for metastatic breast cancer with docetaxel were studied prior to the docetaxel treatment and after the third or fourth course. Autonomic cardiovascular function tests were performed and heart rate and blood pressure variability were assessed with power spectrum analysis. RESULTS: Heart rate variability or the heart rate responses to the autonomic function tests did not change after docetaxel treatment. The blood pressure response to standing was enhanced and systolic blood pressure variability decreased after three to four cycles of docetaxel. CONCLUSIONS: Docetaxel treatment did not deteriorate vagal cardiac control in breast cancer patients after exposure to epirubicin. The observed changes in blood pressure responses suggest that docetaxel changes sympathetic vascular control. However, these changes seem to be related to altered cardiovascular homeostasis rather than peripheral sympathetic neuropathy.

Stratum corneum chymotryptic enzyme in psoriasis.

Stratum corneum chymotryptic enzyme (SCCE) is a serine protease which may function in the turnover of the stratum corneum by means of degradation of intercellular adhesive structures between corneocytes. It is also potentially an epidermal activating enzyme for cytokines such as interleukin-1beta. The aim of this work was to study the expression of SCCE in psoriatic epidermis by means of immunohistochemistry, and to elucidate the nature of the SCCE present in psoriatic scales by means of biochemical analyses. In comparison to normal skin the number of cell layers expressing SCCE in psoriatic lesions was consistently increased. In nonlesional psoriatic skin the pattern of SCCE expression varied. It was similar to the pattern in normal skin in some biopsies, whereas in other biopsies evidence of an increased expression of SCCE was found. By means of zymography and immunoblotting, extracts of psoriatic scales were found to contain active SCCE as well as enzymatically inactive SCCE precursor. Also the effects of inhibitors on the activity towards a chromogenic protease substrate in the extracts after partial purification by gel exclusion chromatography were compatible with the presence of enzymatically active SCCE. We conclude that the expression of SCCE in psoriasis may be upregulated, and that the conversion of inactive SCCE-precursor to active SCCE occurs in the psoriatic lesion. The possible role of SCCE in the pathophysiology of psoriasis remains to be elucidated, but should be considered in future studies.

The effect of estrogen replacement therapy on cardiac autonomic regulation.

OBJECTIVE: To study the effects of estrogen replacement therapy (ERT) and sleep stage on autonomic cardiac regulation. SRUDY DESIGN: Seventy-one healthy postmenopausal women received transdermal ERT and placebo separated by a washout in a randomized, placebo-controlled, double-blind, cross-over trial. Polysomnography was conducted at the end of each treatment. Heart rate variability (HRV) was assessed in epochs of the awake state, stage 2, slow wave and REM sleep. The effects of estradiol and sleep stages on HRV were analyzed. RESULTS: ERT decreased heart rate in the awake state and quiet sleep, but not in REM sleep. ERT did not change the heart rate variability. Heart rate decreased and HRV increased during stage 2 and slow wave sleep compared with the awake state with placebo. In REM sleep, similarly, heart rate increased above awake values and the values of HRV parameters fell back to awake levels. CONCLUSIONS: The results suggest that ERT increases vagal tone, but does not change cardiac vagal modulation. Changes in HRV suggest a strong vagal influence in non-REM and a sympathetic influence in REM sleep.

Periodic spectral components of fetal heart rate variability reflect the changes in cord arterial base deficit values: a preliminary report.

Fetal distress changes the function of the autonomic nervous system. These changes are reflected in the fetal heart rate and can be quantified with power spectrum analysis of heart rate variability. The purpose of this study was to find out whether spectral components of fetal heart rate variability (FHRV) during labor are associated with fetal cord arterial base deficit values at birth. The association between FHRV and umbilical cord arterial base deficit was studied in 14 singleton fetuses with normal pregnancy at 35-40 weeks of gestation. Fetal ECG was recorded by scalp-electrode using a STAN Fetal ECG monitor (Cinventa Ab, Mölndal, Sweden). FHRV was quantified by computing Fast-Fourier-transformed heart rate (HR) spectra at three frequency bands: low-frequency (LF) 0.03-0.07 Hz, mid-frequency (MF) 0.07-0.13 Hz and high-frequency (HF) 0.13-1.0 Hz. We found that total FHRV and MF FHRV were lower in fetuses with cord arterial base deficit 8 to 12 mmol/L in comparison to the fetuses with normal cord arterial base deficit value (P=0.02 and P=0.01, respectively). A linear correlation was found between the spectral densities and the cord arterial base deficit values (r=0.4 and r=0.6, respectively). We conclude that the results suggest changes in the autonomic nervous cardiac control in fetuses with cord arterial base deficit between 8 to 12 mmol/L. The clinical applicability of our observations on FHRV in predicting fetal distress remains to be further studied.

Comparison of cardiovascular reflex tests and blood pressure measurement in prediction of pregnancy-induced hypertension.

A changed pressor response to some cardiovascular reflex tests and an increase in midtrimester blood pressure has been reported to precede the appearance of hypertension in pregnancy-induced hypertensive disorders (PIH). In order to compare the value of midtrimester blood pressure with the cardiovascular reflex tests, in predicting the risk of PIH, the Valsalva manoeuvre, the orthostatic test, the deep breathing test and the isometric handgrip test were performed prospectively in 94 women studied once at 21-29 weeks of pregnancy. Eight subjects developed PIH 3-12 weeks after the testing. The resting blood pressure in midpregnancy was related to PIH later in pregnancy. The most powerful measures were the supine diastolic resting blood pressure (odds ratio, 1.24; 95% confidence limits, 1.08-1.43) and the mean arterial pressure (odds ratio, 1.25; 95% confidence limits, 1.09-1.44). Signs of autonomic dysfunction were found in 37% of the patients developing PIH and in 8% of the healthy remaining subjects (P = 0.04). The results show that the preclinical stage of PIH is associated with some changes in the neural hemodynamic control. However, cardiovascular reflex tests do not add much information on the risk of PIH compared with measuring of the resting blood pressure during mid-pregnancy.

Autonomic cardiovascular control in pregnancy.

Pregnancy is associated with profound adaptive changes in the maternal hemodynamics. Although the autonomic nervous system plays a central role in the adaptation of the cardiovascular system to various needs, its role in the adaptation of the circulation to the demands of pregnancy is poorly understood. This paper reviews the literature of autonomic cardiovascular control in pregnancy as studied with the cardiovascular reflex tests. A Medline search and manual cross-referencing for prior publications were used. All papers found on the hemodynamic effects of the Valsalva maneuver, the orthostatic test, the deep breathing test, the isometric handgrip test and maternal heart rate variability in pregnancy were reviewed and all publications that studied short-term changes in maternal heart rate and blood pressure were included. The beginning of pregnancy is associated with sympathetic reactivity, whereas the latter half of pregnancy is characterized by increased hemodynamic stability during orthostatic stress. The heart rate response to the Valsalva maneuver is blunted in mid-pregnancy, possibly due to changes in the baroreflex and increased maternal blood volume. Heart rate variability is significantly reduced in the second trimester. Cardiovascular reflex tests can be used to study drug effects on maternal circulation non-invasively.

Valsalva manoeuvre can be used to study baroreflex sensitivity in pregnancy.

OBJECTIVE: The aim of this study was to assess whether baroreflex sensitivity can be measured in a non-invasive manner with the Valsalva manoeuvre in pregnancy. STUDY DESIGN: Baroreflex sensitivity was measured from the reflex response to phenylephrine injection and phase four of the Valsalva manoeuvre in nine pregnant women at 27 (range 24-33) gestational weeks. RESULTS: Both the phenylephrine test and the Valsalva manoeuvre yielded similar estimates of baroreflex sensitivity (9.3 (4.1) ms/mmHg vs. 8.0 (5.2) ms/mmHg, Pearson's correlation coefficient r = 0.81, P < 0.008, linear regression BRSValsalva (ms/mmHg) = 1.03 x BRSPhenylephrine + 1.59). Comparable changes in heart rate and blood pressure were obtained with the phenylephrine test and the Valsalva manoeuvre. CONCLUSION: The physiological challenge caused by the Valsalva manoeuvre can be used to measure baroreflex sensitivity in pregnancy. A possibility to study baroreflex function non-invasively, without pharmacological intervention, benefits future research of blood pressure regulation in pregnancy.

Expert consensus in solo voice performance evaluation.

Experts were interviewed to identify criteria for evaluation of vocal performance. A scale was then constructed and inter- and intrajudge reliability assessed. Experts listened to 19 different performances, plus 6 presented a second time. Interjudge reliability for one judge was modest, but increased dramatically as the size of the judge panel increased. The most reliable items were overall score and intonation accuracy. Diction was less reliable than other items. Intrajudge reliability was higher for overall score than for any other item. A factor analysis on the test items yielded factors labelled intrinsic quality, execution, and diction. Another factor analysis, using the experts as variables, revealed two underlying evaluative dimensions. It was found that 13 experts were primarily influenced by execution, and that 8 were mainly affected by intrinsic quality. Interjudge and intrajudge reliabilities of these two groups differed.