Single serum progesterone as a screen for ectopic pregnancy: exchanging specificity and sensitivity to obtain optimal test performance

OBJECTIVE: To investigate the diagnostic accuracy of screening serum P in diagnosis of ectopic pregnancy (EP) and to identify a cutoff value that provides the best compromise between test sensitivity and specificity. DESIGN: Retrospective analysis. SETTING: University hospital. INTERVENTIONS: Observation only. PATIENTS: First trimester pregnant women at risk for EP. MAIN OUTCOME MEASURE: Single P measurements were obtained from 3,674 pregnancies with outcomes defined as EP, viable intrauterine pregnancy (IUP), and spontaneous abortion (SAB). Diagnostic accuracy of the test was analyzed by generating receiver operating characteristic (ROC) curves, which quantify the ability of the test to distinguish EP and SAB from IUP. RESULTS: Diagnostic accuracy for EP versus IUP was 88.7% +/- 0.1% (mean +/- SEM); for SAB versus IUP, 93.8% +/- 0.4%; and for SAB + EP versus IUP, 92.8% +/- 0.4%. Diagnostic accuracy for SAB versus EP was only 39.4% +/- 0.2%. In the interval of 15.0 to 19.9 ng/mL (47.7 to 63.3 nmol/L), P missed 5.3% of the EPs and incorrectly included 84.3% of the viable IUPs; in the interval of 20.0 to 24.9 ng/mL (63.6 to 79.2 nmol/L), sensitivity improved in that only 3.5% of the EPs were missed but 88.8% of viable IUPs were included incorrectly. A cutoff value of > or = 17.5 ng/mL (55.7 nmol/L), the median point of the 15.0 to 19.9 ng/mL (47.7 to 63.3 nmol/L) interval, missed only 35 of 423 (8.3%) total EPs in the study. CONCLUSION: Analysis of ROC curves demonstrates that single serum P has high diagnostic accuracy for differentiating accidents of pregnancy (SAB and EP) from viable IUP, both individually (SAB versus IUP and EP versus IUP) and collectively (SAB + EP versus IUP); it cannot efficiently discriminate SAB versus EP. We conclude that for P > or = 17.5 ng/mL (55.7 nmol/L), patients thought to be at risk for EP may be followed reasonably without ultrasound or further invasive diagnostic studies.     

Changes in levels of cell adhesion molecules, acute phase proteins, lipids and hemostasis in relation to levels of endogenous estrogens during pregnancy and after ovariectomy

The protective effect of oestrogens is probably caused also by the active inhibition of the inflammatory reaction of the acute phase and release of inflammatory cytokines type IL-1 beta or TNF-alpha by this hormone. We formulated this hypothesis because we recorded a drop of the protein of the acute stage, orosomucoid, in relation to the rising oestrogen level during pregnancy (r = -0.511, p < 0.0001). It ensues also from the finding of a lower level of cytoadhesive molecules of sE-selectins in a group of 66 pregnant women (sE-sel.: 32.95 +/- 12.5 ng/ml) with a higher level of 17-beta estradiol (17-beta E2: 9.34 +/- 7.8 nmol/l), as compared with the sE-selectin level in a group of 14 women after ovariectomy (sE-sel.: 43.97 +/- 8.174 ng/ml, p < 0.016) who lacked oestrogen (17-beta E2 0.14 +/- 0.13 nmol/l) and in a group of pregnant women (n 19) in the first trimester with level of 17-beta E2: 1.89 +/- 0.711 nmol/l where the sE-selectin concentrations at the onset pregnancy was higher (sE-sel.: 35.59 +/- 9.5 ng/ml) than in a group of pregnant women (n 38) during the second and third trimester (sE-sel.: 30.58 +/- 13.3 ng/ml, p < 0.05) with 17-beta E2 concentration 11.96 +/- 7.18 ng/ml. The finding of lower sE-selectin levels which is a sign that the endothelium is not exposed to the action of inflammatory cytokines IL-1 or TNF may thus be associated with the active "control" of thrombophilia in pregnancy. When during pregnancy in conjunction with oestrogen levels changes in the lipid concentration were investigated a compensating mechanism could be observed. Hypercholesterolaemia and hypertriglyceridaemia in pregnant women was associated with a rise of oestrogen levels as well as of "cardioprotective" HDL-cholesterol (the HDL level was during the first trimester 1.31 +/- 0.26 nmol/l, in the second and third trimester 1.69 +/- 0.48 nmol/l, p < 0.0167).     

Altered cellular calcium responsiveness to insulin in normal and hypertensive pregnancy

OBJECTIVE: To investigate the glucose-independent calcium-related effects of insulin from subjects with normal and hypertensive pregnancies. METHOD: We used lndo-l fluorescence spectroscopy to measure cytosolic free calcium levels (Cai) in peripheral blood mononuclear cells (PBM) from 17 women (aged 20-40 years), six nonpregnant controls (NPC), five pregnant normotensive (PNT) women and six pregnant hypertensive (PHT) women, before and 5, 30, 60, 120 and 180 min after in vitro incubation with 200 microU/ml insulin. RESULTS: Basal Cai levels were significantly higher in PHT women (175.2 +/- 18.8 nmol/l) than they were in NPC women (122.8 +/- 2.8 nmol/l) and PNT women (123.9 +/- 3.5 nmol/l). The initial insulin-induced rise in Cai was similar in NPC (delta Cai 13.5 +/- 5.6 nmol/l) and PNT women (delta Cai 14.6 +/- 3.7 nmol/l), but appeared blunted in PHT women (delta Cai 8.2 +/- 3.5 nmol/l), and, for all pregnant subjects, was closely and inversely related to basal Cai. Over time, in PNT women, delta Cai did not increase from the initial response (maximal delta Cai 20.5 +/- 2.3 nmol/l) compared to NPC. The total cellular calcium response to insulin was also blunted in PNT women (the area under the calcium-responses curve was 86 +/- 3.4 versus 97.4 +/- 6.5 nmol/l), but was excessive in PHT women (115.5 +/- 6 nmol/l, P = 0.05). CONCLUSIONS: Hypertension in pregnancy is associated with excess Cai, insulin raises Cai in PBM, and different alterations of Cai responsiveness to insulin occur both in normal and in hypertensive pregnancy. These cellular calcium alterations may help to explain altered tissue responsiveness to insulin and other hormones in pregnancy.     

Paget disease of the calcaneus: findings on MR imaging

The aim of the current study was to examine whether the measurement of intrauterine human decidua-associated protein (hDP) 200 might be of clinical value in the diagnosis of ectopic pregnancy versus early missed abortion. Uterine fluid levels of hDP 200 were measured in two groups of patients: 20 women with ectopic pregnancy, diagnosed by laparoscopy, and 20 women diagnosed (after curettage) as having a missed abortion. No significant difference in hDP 200 levels was observed comparing patients with ectopic pregnancy (mean 114.0+/-58.2 mU/ml) and patients with early missed abortion (mean 222.0+/-116.0 mU/ml), although a trend towards lower levels of uterine fluid hDP 200 was noted in the group of patients presenting with tubal pregnancy. Thus, according to our data, intrauterine hDP 200 is not sufficiently discriminative to be of clinical value in the diagnosis of ectopic pregnancy.     

Prolactin levels in pregnant women with glucose intolerance at full-term delivery

A prospective study was carried out to establish the influence of deteriorated metabolism of glucose in mothers to the synthesis and secretion of prolactin during the pregnancy. The examination included a 101 pregnant women with delivery term between 259 and 287 day of gestation; 36 pregnant women manifested glucose intolerance or diabetes during the pregnancy and 12 of them also had marked signs of gestation. Control group consisted of 65 pregnant women. The level of prolactin in the sera of mothers with glucose intolerance (205.7 +/- 66.4 micrograms/l) was significantly increased (p < 0.05) than in case of mothers with normal pregnancy (172.2 +/- 60.7 micrograms/l), probably due to the development of gestosis in a large number of pregnant women. The difference of prolactin level in pregnant women with glucose intolerance but without the elements of gestosis (167.3 +/- 35.7 micrograms/l) and in women with normal pregnancy was not important. The difference of prolactin level in the serum of umbilical artery (245.5 +/- 101.2 micrograms/l and 261.0 +/- 78.8 micrograms/l) and in amniotic fluid (428.6 +/- 161.1 micrograms/l and 422.9 +/- 112.9 micrograms/l) was not of statistical significance. Pregnant women with glucose intolerance and elements of gestosis had significantly higher concentration (p < 0.05) in the serum of the mother, in the serum of umbilical artery and in the serum of amniotic fluid (282.4 +/- 41.6 micrograms/l, 315.6 +/- 103.3 micrograms/l and 460.4 +/- 130.2 micrograms/l) than the pregnant women with glucose intolerance but without elements of developing gestosis (167.3 +/- 35.7 micrograms/l, 210.5 +/- 81.5 micrograms/l, and 402.6 +/- 118.8 micrograms/l). There was no evidence of the functional connection between prolactin and glucose metabolism.     

Bacillus thermoamyloliquefaciens KP1071 alpha-glucosidase II is a thermostable M(r) 540,000 homohexameric alpha-glucosidase with both exo-alpha-1,4-glucosidase and oligo-1,6-glucosidase activities

The lethality of acute renal failure exceeds 50% due to multiorgan dysfunction. In such critically ill patients a reduction of thyroid hormone concentrations without clinical symptoms or laboratory evidence of hypothyroidism frequently occurs. Selenium has recently been shown to play a major role in thyroid hormone metabolism. The aim of this study was to investigate the possible influence of selenium on thyroid hormone metabolism in acute renal failure. Changes in thyroid metabolism were related to the severity of multiorgan failure and to the clinical course. Thyroxine (T4), tri-iodothyronine (T3), free-T4, free-T3, thyrotropin (TSH), serum creatinine, and plasma selenium concentrations in 28 patients (mean age 60 +/- 13) with acute renal failure and multiple-organ dysfunction syndrome were determined initially, and every 3 days after hospital admission. The plasma selenium concentration was found to be reduced compared to normal controls (32 +/- 14 vs. 70-120 micrograms/L). T4 (56 +/- 15 nmol/L, normal range 64-148), T3 (1.31 +/- 0.38 nmol/L, normal range 1.42-2.46), free-T3 (3.1 +/- 1.0 pmol/L, normal range 4.7-9.0), and free-T4 (10.8 +/- 4.0 pmol/L, normal range 10.3-25.8) values were low in 50-70% of the patients at the time of presentation. Plasma TSH concentrations were within the normal range (0.59 +/- 0.79 mU/L, normal range 0.25-3.1), and no clinical symptoms of hypothyroidism were observed. T4 concentration was higher in patients who survived acute renal failure compared to nonsurvivors (62 +/- 22 vs. 51 +/- 16 nmol/L, p < 0.05). Plasma selenium concentration was lower in patients with a severe organ dysfunction syndrome (36 +/- 10 vs. 29 +/- 19 micrograms/L) and correlated with the number of organ failures in these patients (r = -0.247, p < 0.05). T4 and free-T4 values paralleled decreasing selenium concentrations (r = 0.35, p < 0.05). Thyroid hormone levels were reduced in patients with acute renal failure without an increase in TSH. An increase in T4 concentrations became apparent during treatment and may be related to a favorable outcome in acute renal failure. Thyroid hormone concentrations paralleled plasma selenium levels, indicating a possible influence of selenium on thyroid function in acute renal failure.     

Development of rotational digital angiography and new cone-beam 3D image: clinical value in vascular lesions

There are no data in the literature on effects of supplementing infants with yeast-selenium. We therefore studied the impact of selenium-enriched yeast on the serum selenium concentration of preterm infants living in a selenium-low area (Hungary). Twenty-eight preterm infants with a mean +/- SD birthweight of 962 +/- 129 g and a gestational age of 27 +/- 1 weeks were randomized into two groups at birth with respect to selenium supplementation. In the supplemental group (n = 14) infants received 4.8 mg yeast containing 5 microgram selenium daily with naso-gastric drip during the first 14 postnatal days. The nonsupplemented infants were used as a reference group. In the supplemented group the serum selenium concentration increased from 32.1 +/- 8.5 microgram/l to 41.5 +/- 6.5 microgram/l and in the nonsupplemented group it decreased from 25.9 +/ 6.8 microgram/l to 18.2 +/- 6.4 microgram/l within two weeks. The serum glutathione peroxidase activity increased from 2.97 +/- 0.73 U/20 microliter to 6.42 +/- 3.11 U/20 microliter in the supplemented group, and it did not change significantly (from 3.53 +/- 0.94 U/20 microliter to 3.85 +/- 0.95 U/20 microliter) in the nonsupplemented group. We did not observe any complications or side effects in connection with enteral yeast-selenium supplementation. It is concluded that selenium-enriched yeast is a safe and an effective form of short term enteral selenium supplementation for preterm infants.     

Annual variations in serum thyroid-stimulating hormone and thyroid hormones and in their responses to thyrotrophin-releasing hormone in the reindeer

The reindeer in its natural habitat is subject to great annual variations in ambient temperature, illumination and nutrition. To ascertain the effect of these environmental factors on thyroid function, serum thyroid-stimulating hormone (TSH), thyroxine (T4), tri-iodothyronine (T3) and reverse T3 (rT3) concentrations were measured four times a year (2 June, 8 October, 21 November, and 24 February) in 14 animals housed outdoors at latitude 69 degrees 10'N. They all showed statistically significant (P < 0.05) seasonal changes. Serum TSH and T4 were highest in February (623 +/- 30 ng/ml and 287 +/- 19 nmol/l respectively). TSH was lowest in October (318 +/- 47 ng/ml) and T4 in November (199 +/- 19 nmol/l). The T3 concentration was highest in November (3.0 +/- 0.3 nmol/l) and lowest in June (1.8 +/- 0.2 nmol/l). In contrast, rT3 was highest in June (3.6 +/- 1.2 nmol/l) and lowest in November (1.9 +/- 0.6 nmol/l). Thus, there was an inverse relationship between T3 and rT3 (linear regression r = -0.406, P < 0.01). TSH, T4, T3 and rT3 responses to exogenous thyrotrophin-releasing hormone (synthetic TRH; 500 micrograms i.m.) were determined in ten animals. The magnitude of their response to TRH was significantly (P < 0.05) dependent on the time of year. When compared with the control level all the parameters rose significantly (P < 0.05). The greatest rise in serum TSH occurred in October (219 +/- 151%) and the smallest in February (66 +/- 53%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Do androgens regulate growth hormone-binding protein in adult man?

To determine whether adult serum GH-binding protein (GHBP) is regulated by androgen, serum GHBP concentrations were compared between 20 normal and 18 hypogonadal men matched for age and body mass index, and the effect of im testosterone treatment (250 mg testosterone enanthate) on GHBP levels in the 18 hypogonadal men was studied. Nine of the hypogonadal subjects had coexistent GH deficiency. Serum GHBP concentration was measured by a ligand immunofunctional assay. The mean serum GHBP level in untreated hypogonadal men was not significantly different from that of normal men (0.98 +/- 0.15 vs. 1.17 +/- 0.16 nmol/L). The mean serum insulin-like growth factor I (IGF-I) level was significantly lower in the hypogonadal men (132 +/- 22 vs. 206 +/- 17 ng/mL; P < 0.01). Basal testosterone (3.7 +/- 0.7 nmol/L) in hypogonadal men increased during treatment to a mean level of 29.1 +/- 2.8 nmol/L, which was not significantly higher than that in normal men (22.6 +/- 1.9 nmol/L). The mean serum GHBP level in hypogonadal men fell significantly during treatment to 0.60 +/- 0.11 nmol/L (P = 0.0003), whereas the serum IGF-I level rose significantly to 151 +/- 26 ng/mL (P < 0.04). The decrease in GHBP level was significant in both the GH-sufficient and GH-deficient subjects (P < 0.02 in both instances), whereas the increase in IGF-I level was significant in the GH-sufficient group (199 +/- 22 to 235 +/- 29 ng/mL; P < 0.04) but not in the GH-deficient group (53 +/- 7 to 55 +/- 5 ng/mL; P > 0.8). Thus, serum GHBP is normal in hypogonadal men but is reduced by testosterone treatment irrespective of endogenous GH-secretory status. It was concluded that the effect of testosterone on GHBP is pharmacological and occurs independent of GH mediation.     

Long-term follow-up (8 to 17 years) after thromboexclusion operation for thoracic aortic aneurysms

Forty-eight Russell's viper bite patients (40 males, 8 females), age ranging from 16-76 years were studied. Out of 48 patients, 14 were found to have a prolonged whole blood clotting time test (WBCT) (i.e. incoagulable blood) (Group 1); 23 had a normal WBCT (i.e. clotted blood) (Group II); and 11 patients had a normal WBCT on admission which changed to non-clotting during the clinical course (Group III). Four patients from group I developed hypotension and 2 expired. The serum cortisol concentration (mean +/- SEM) on admission among groups I and II were 639 +/- 45.6 and 424 +/- 33.2 nmol/l respectively. The blood cortisol level in 35 subjects (controls) were 370.7 +/- 17.7 nmol/l (mean +/- SEM). There was a significant rise of blood cortisol in patients with incoagulable blood when compared to controls at the time of admission to the hospital (p < 0.05); but there was no significant difference among those patients with clotted blood. A much higher mean serum cortisol level was observed in 4 patients with hypotension as compared to 10 patients without shock. These patients with hypotension according to our study shown to have a favorable response to steroid therapy and eventually recovered. Whether higher doses of steroid in addition to antiserum confer extra benefit in suppressing nonspecific venom effects on the pituitary and/or adrenal is not known.     

Vitamin D deficiency among hospitalized and home-bound elderly

Vitamin D status, measured as serum calcidiol concentration, was studied in a group of 273 recently hospitalised patients at Aker University Hospital and compared to a group of 98 persons living in their own homes, all living in Oslo and all above 70 years of age. We found lower serum calcidiol concentrations in the hospital group than among people living in their own homes, in men as well as in women (mean +/- SD, 40.4 nmol/l +/- 23.2 vs 59.6 nmol/l +/- 28.9 in men and 37.5 nmol/l +/- 22.6 vs 48.5 +/- 20.3 in women). 34% of the men and 49% of the women in the hospital group had vitamin D deficiency (se. calcidiol < 20 nmol/l). There was no seasonal variation in the hospitalised group; the group living at home did show seasonal variations, with highest levels in late autumn (62.2 nmol/l) and lowest levels in February (42.7 nmol/l). The low levels of calcidiol concentration may contribute to the high prevalence of hip-fracture among elderly in Oslo.     

Determination of DMPC hydration in the L(alpha) and L(beta'') phases by 2H solid state NMR of D2O

OBJECTIVE: To compare the effect of vaginal misoprostol with that of placebo when used prior to dilation and aspiration in women with a missed abortion. METHOD: Eighty-four pregnant women with a missed abortion were randomized to receive either vaginal misoprostol (200 micrograms) or placebo the day before the planned dilatation and aspiration under inhalation anesthesia. RESULT: Thirty-five women (83.33%) in the misoprostol group and 6 women (17.14%) in the placebo group aborted spontaneously prior to the scheduled dilatation and aspiration, P < 0.0001. The mean insertion to spontaneous expulsion time was 11.63 +/- 6.14 h in the misoprostol group compared to 11.95 +/- 5.43 h in placebo. In the misoprostol group two women required intramuscular pethidine for analgesia. In the placebo group there were two cases of blood loss in excess of 500 ml and one woman with a uterine perforation. CONCLUSION: Vaginal administration of misoprostol to women with a missed abortion produced spontaneous expulsion of the pregnancy and reduced the need for surgical treatment.     

Erythrocyte sodium lithium countertransport in normal and hypertensive pregnancy: relation to haemodynamic changes

OBJECTIVE: To establish the changes in erythrocyte sodium lithium countertransport (SLC) with advancing normal pregnancy and to determine if these changes were different in pregnancy induced hypertension (PIH). The changes in both groups were assessed in relation to haemodynamic changes. DESIGN: SLC, mean arterial pressure (MAP), cardiac output (CO) and total peripheral vascular resistance (TPVR) were determined serially during normal pregnancy and cross-sectionally in PIH. Women were studied again 20 weeks after delivery where possible. SETTING: Routine antenatal clinic and antenatal ward of a regional reference centre. SUBJECTS: Fifty-one normal primigravid women were studied serially and 41 primigravid women with PIH were studied at time of diagnosis. RESULTS: During normal pregnancy SLC (mmol Li/h/l cells) increased from a nonpregnant value of 0.24 +/- 0.02 (mean +/- SEM) to 0.32 +/- 0.02 at 14 weeks, and 0.37 +/- 0.02 at 20 weeks gestation. This was maintained until 38 weeks (0.40 +/- 0.02). The increase until 20 weeks occurred at the time of greatest change in CO (5.10 +/- 0.18 to 6.79 +/- 0.20 l/min) and TPVR (1327 +/- 58 to 969 +/- 33 dyn/s/cm-5). The decrease in TPVR with a rise in SLC is opposite to the relation reported in essential hypertension so that a functional relation is unlikely. However, the changes within pregnancy were positively correlated (r = 0.43, P < 0.01). In hypertensive pregnancies TPVR was elevated compared with normotensive pregnancies (1543 +/- 100 vs 1090 +/- 37) but the SLC was not different from that found in normotensive pregnancies (0.43 +/- 0.02 vs 0.40 +/- 0.02). CONCLUSIONS: The changes in SLC activity suggest dynamic effects on erythrocyte membrane function during pregnancy. However, no differences could be found between normal and hypertensive pregnancy and SLC is unlikely to be of value as a marker of hypertensive risk during pregnancy.     

Determination of free follistatin levels in sera of normal subjects and patients with various diseases

We developed an assay system for measuring free follistatin by using an anti-follistatin mouse monoclonal antibody and [125I]activin A. The sensitivity of this assay was 0.5 microgram/l and cross-reactivities with inhibin, luteinizing hormone, follicle-stimulating hormone and growth hormone were all less than 0.5%. The dose-response curves of human sera and follicular fluid were parallel to the standard curve, and the follicular fluid contained a large amount of follistatin (6.4 +/- 0.5 mg/l, mean +/- SEM; N = 13). The within- and between-assay coefficients of variation calculated from the analysis of serum samples of four different concentrations were 3.3-7.8% and 3.9-11.0%, respectively. The recovery rates of free follistatin at five different doses were 86.4 - 102.4%. When activin A was added to the same sample, free follistatin recovery rate declined dose-dependently. Gel filtration analyses of human serum and follicular fluid resulted in a single peak corresponding to authentic follistatin. Using this assay, free follistatin concentrations in sera were measured in normal, pregnant and diseased subjects. The free follistatin level in serum of normal adults was 3.5 +/- 0.2 micrograms/l (N = 60), which was significantly elevated in pregnant women (16.7 +/- 1.3 micrograms/l, N = 56), and in patients with chronic liver disease (8.1 +/- 1.1 micrograms/l, N = 20), chronic renal failure (6.7 +/- 0.9 micrograms/l, N = 42), advanced solid cancer (8.5 +/- 1.0 micrograms/l, N = 39) and hematological malignancies (6.8 +/- 1.0 micrograms/l, N = 18). These data indicated that the free follistatin concentration in serum is detectable and varies during pregnancy and in various diseased states.     

Stapled hemorrhoidectomy for the treatment of hemorrhoids

The main objective of the present study was to examine the alterations in plasma total homocysteine (tHcy) concentrations during a testosterone-deficient state and after gonadotropin treatment for 6 Months in patients with idiopathic hypogonadotropic hypogonadism (IHH). Thirty-five newly diagnosed male patients with IHH (mean age 21.34+/-1.53 years) and 29 age- and body mass index-matched healthy males (mean age 21.52+/-1.77 years) were recruited into the study. Pretreatment levels of free testosterone (1.51+/-0.66 pg/ml), estradiol (21.37+/- 4.37 pg/ml), FSH (0.91+/-0.24 IU/l) and LH (1.25+/- 0.53 IU/l) were lower than controls (25.17+/-3.06 pg/ml, 31.00+/-4.96 pg/ml, 3.14+/-1.62 IU/l and 4.83+/-1.65 IU/l respectively) (P<0.001). They increased significantly after treatment (18.18+/-1.59 pg/ml, 27.97+/- 4.25 pg/ml, 2.41+/-0.27 IU/l and 2.79+/-0.19 IU/l respectively) (P<0.001). Patients with IHH had lower tHcy levels than controls (10.14+/-1.34 and 12.58+/- 2.29 micro mol/l respectively) (P<0.001). Plasma tHcy concentrations increased significantly (12.63+/-1.44 micromol/l) after 6 months of treatment (P<0.001). As compared with the controls, pretreatment levels of serum creatinine (63.54+/-13.01 vs 82.84+/-16.69 micromol/l), hemoglobin (12.98+/-0.56 vs 13.83+/-0.71 g/dl) and hematocrit (39.29+/-2.01 vs 41.38+/-1.95%) were significantly lower (P<0.001), and they increased significantly following treatment (80.24+/-11.93 micromol/l, 13.75+/-0.49 g/dl and 41.26+/-1.78% respectively) (P<0.001). The pretreatment folic acid and vitamin B(12) levels were significantly higher in patients when compared with controls (14.87+/-5.68 vs 12.52+/-4.98 nmol/l, P=0.034 and 289.75+/-92.34 vs 237.59+/-108.17 pmol/l, P=0.002 respectively). They decreased significantly after treatment (11.29+/-3.31 nmol/l and 228.51+/-54.33 pmol/l respectively) (P<0.001). The univariate and multivariate regression analysis results showed that only changes in creatinine, creatinine clearance, vitamin B12 and folic acid were independently associated with changes in tHcy levels in patients with IHH. In conclusion, the increase in plasma tHcy concentrations following gonadotropin treatment seems to be largely independent of changes in androgen levels.     

Elevated levels of bile acids in colostrum of patients with cholestasis of pregnancy are decreased following ursodeoxycholic acid therapy [see comemnts

BACKGROUND/AIMS: Intrahepatic cholestasis of pregnancy is characterised by increased levels of serum bile acids. Ursodeoxycholic acid therapy corrects the serum bile acid profile. The aims of this study were: (i) to investigate bile acid excretion into colostrum of women with intrahepatic cholestasis of pregnancy; (ii) to compare concentrations of bile acids in serum and colostrum of non-treated and ursodeoxycholic acid-treated patients; and (iii) to clarify whether ursodeoxycholic acid is eliminated into colostrum following treatment. METHODS: Bile acids were assessed by gas chromatography and high-performance liquid chromatography in serum collected at delivery, and in colostrum obtained at 2+/-1 days after labour, from patients with intrahepatic cholestasis of pregnancy, non-treated (n=9) and treated (n=7) with ursodeoxycholic acid (14 mg/kg bw per day, for 14+/-7 days) until parturition. RESULTS: The concentration of total bile acids in colostrum from patients with intrahepatic cholestasis of pregnancy was higher than in normals (23.3+/-14.8 micromol/l vs. 0.7+/-0.2 micromol/l, p<0.01) and cholic acid was a major species (19.0+/-13.1 micromol/l), reflecting the elevated concentrations in maternal serum (48.9+/-21.0 micromol/l, total bile acids; 33.9+/-16.7 micromol/l, cholic acid. Following ursodeoxycholic acid administration, total bile acids and cholic acid levels in colostrum diminished to 5.7+/-2.5 micromol/l and 3.6+/-1.5 micromol/l, respectively; the proportion of cholic acid decreased (60.6+/-8.0% vs. 76.8+/-5.0%, p<0.05). The ursodeoxycholic acid concentration in colostrum was maintained following treatment; its increased percentage (9.4+/-3.2% vs. 1.0+/-0.2%, p<0.01) was still lower than in maternal serum (20.8+/-3.6%, p<0.05). Only a small proportion (<1%) of lithocholic acid was found in colostrum following therapy. CONCLUSIONS: Bile acid concentrations are elevated and cholic acid is the major species accumulating in colostrum, reflecting serum bile acid profiles in intrahepatic cholestasis of pregnancy. Ursodeoxycholic acid therapy decreases endogenous bile acid levels in colostrum.     

Blunted cortisol response after administration of corticotropin releasing hormone in endotoxemic dogs

To evaluate the effects of a standard inflammatory challenge on the dynamics of the hypothalamic-pituitary-adrenal (HPA) axis, we studied the effects of low-dose endotoxin (1.0 microgram/kg) on plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations in a saline-controlled study in five awake dogs. Four hours after endotoxin or saline challenge human corticotrophin-releasing hormone (hCRH; 1.0 microgram/kg) was administered. Plasma ACTH and cortisol levels increased considerably in response to endotoxin, from 13 +/- 1 ng/l to 360 +/- 85 ng/l (p < 0.01) and from 60 +/- 20 nmol/l to 710 +/- 80 nmol/l (p < 0.01). Despite a considerable difference in ACTH and cortisol levels prior to CRH administration between both studies (p < 0.01), the absolute increase in ACTH levels induced by hCRH was not different (231 +/ 43 ng/l vs 238 +/- 45 ng/l, control vs endotoxin). Plasma cortisol levels increased significantly in the control study (from 40 +/- 10 nmol/l to 330 +/- 40 nmol/l, p < 0.01), whereas they did not change in the endotoxin study after hCRH administration (from 710 +/- 80 nmol/l to 730 +/- 70 nmol/l, ns). We conclude that the HPA-axis reacts initially to endotoxin in such a way that cortisol, but not ACTH, secretion is maximized. Therefore, a blunted cortisol response to CRH testing is part of the initial response to infection.     

Gestation increases nitric oxide-mediated vasodilation in rat uterine arteries

OBJECTIVE: The purpose of this study was to determine the influence of endothelium-released nitric oxide on uterine arterial tone and reactivity during pregnancy. STUDY DESIGN: The effects of pregnancy on endothelial function were evaluated in isolated pressurized rat uterine arteries from late-pregnant rats (day 19 to 20) versus age-matched nonpregnant controls. The effects of nitric oxide synthase inhibition (N(omega)-nitro-L-arginine) on arterial tone and reactivity under basal and activated (phenylephrine) conditions were determined, as was arterial reactivity to endothelium-dependent (acetylcholine) and endothelium-independent (sodium nitroprusside) vasodilators, by evaluating changes in lumen diameter. RESULTS: (1) Maximal constriction to N(omega)-nitro-L-arginine was significantly enhanced under basal (nonstimulated) conditions in arteries from late-pregnant versus nonpregnant rats (changes in lumen diameter 37% +/- 8% vs 9.3 +/- 6.2%, respectively, p < 0.05). (2) Nitric oxide synthase blockade with 1 nmol/L N(omega)-nitro-L-arginine significantly increased phenylephrine sensitivity in arteries from late-pregnant animals (median effective concentration 115 +/- 23 nmol/L vs 33 +/- 8 nmol/L, control vs treated vessels, p < 0.05) but was without statistically significant effect on arteries from nonpregnant animals (control 255 +/- 164 nmol/L, treated 250 +/- 102 nmol/L, p > 0.05). (3) The threshold concentration of acetylcholine required to elicit endothelium-dependent dilation was significantly lower in late-pregnant versus nonpregnant arteries (1.4 +/- 0.2 nmol/L vs 12.2 +/- 3.8 nmol/L, p < 0.05). (4) Vascular smooth muscle sensitivity to an exogenous nitrodilator (sodium nitroprusside) was identical in late-pregnant versus nonpregnant vessels. CONCLUSION: Endothelial vasodilator influences are augmented during pregnancy under basal, activated (phenylephrine), and chemically provoked (acetylcholine) conditions in uterine arteries by enhanced release of nitric oxide.     

The changes of lipid metabolism and hemorrheology in intrahepatic cholestasis during pregnancy

OBJECTIVE: To identify the influence of the increased level of serum cholyglycine (CG) on lipid metabolism and hemorrheology in patients with intrahepatic cholestasis during pregnancy (ICP). METHODS: The concentrations of serum CG, total cholesterol (CH), triglycerides (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), high shear and low shear of blood specific viscosity (HS and LS), plasma specific viscosity (PV) and hematocrit (HCT) were measured in 68 cases of primiparas with single pregnancy and 30 healthy nonpregnant women respectively. The group of ICP was composed of 35 cases with CG > 6 mumol/L, the group of normal pregnancy, 33 cases with CG < 6 mumol/L. RESULTS: The means of CG and the lipidic parameters in the two pregnant groups were significantly higher than those in the non-pregnancy group (P < 0.02-0.001) except the means of HDL-C between the groups of ICP and non-pregnancy. The levels of LDL-C, LDL-C/HDL-C, LS, PV and HCT in the ICP were significantly higher than those in the normal pregnancy group (P < 0.02-0.001). CONCLUSIONS: There are significant changes of lipid metabolism and hemorrheology in patients with ICP. However, these changes could be corrected after pregnancy termination, when the level of serum CG returned to normal. The results suggest that the pathophysiologic changes of ICP are associated with increased level of serum CG.     

17 alpha-Hydroxyprogesterone responses to leuprolide and serum androgens in obese women with and without polycystic ovary syndrome offer dietary weight loss

Insulin resistance and increased ovarian cytochrome P450c17 alpha activity (i.e. increased 17 alpha-hydroxylase and, to a lesser extent, increased 17,20-lyase) are both features of the polycystic ovary syndrome (PCOS). Evidence suggests that hyperinsulinemia may stimulate ovarian P450c17 alpha activity in obese women with PCOS. We hypothesized that weight loss would decrease serum insulin and P450c17 alpha activity in PCOS. Therefore, we measured serum steroid concentrations and 17 alpha-hydroxyprogesterone responses to leuprolide administration and performed oral glucose tolerance tests before and after 8 weeks of a hypocaloric diet in 12 obese women with PCOS (PCOS group) and 11 obese women with normal menses (control group). Serum insulin decreased in both groups. In the PCOS group, basal serum 17 alpha-hydroxyprogesterone decreased from 4.2 +/- 0.6 to 3.0 +/- 0.5 nmol/L (P < 0.05), and leuprolide-stimulated peak serum 17 alpha-hydroxyprogesterone decreased from 14.9 +/- 2.6 to 8.9 +/- 0.8 nmol/L (P < 0.025). Serum testosterone decreased from 2.47 +/- 0.52 to 1.56 +/- 0.33 nmol/L (P < 0.05), and free testosterone decreased from 9.03 +/- 1.39 to 5.95 +/- 0.50 pmol/L (P < 0.02). None of these values changed in the control group. Serum sex hormone-binding globulin increased by 4.5- and 3-fold in the PCOS (P < 0.003) and control (P < 0.007) groups, respectively. We conclude that dietary weight loss decreases ovarian P450c17 alpha activity and reduces serum free testosterone concentrations in obese women with PCOS, but not in obese ovulatory women. The changes in women with PCOS may be related to a reduction in serum insulin.