Ectopic pregnancies during use of low-dose progestogens for oral contraception

Ectopic pregnancies were studied in two Finnish hospitals in the years 1973 – 1976. A total of 238 cases was found. Of these, 30 (12.6 %) occurred in woman using low-dose progestogens for oral contraception. When sales figures for different progestogens sold in the areas served by the hospitals were obtained, the risk of ectopic pregnancy could be assessed for each progestogen. The risk factor was found to be 1 ectopic pregnancy in 1170 women years with lynestrenol 0.5 mg, 1/290 with norethisterone 0.3 mg, and 1/250 with d-norgestrel 0.03 mg. Lynestrenol 0.5 mg carries a significantly lower risk of ectopic pregnancy (p < 0.01) than other progestogens.     

Maternal serum copper and zinc concentrations in normal and small-for-date pregnancies

Serum concentrations of copper (Cu) and zinc (Zn) were determined in 20 non-pregnant healthy menstruating women and in 20 pregnant women during the 1st, 2nd and 3rd trimesters and 5 weeks postpartum as a longitudinal study. Also a cross-sectional population of 106 women was studied. Further, Cu and Zn concentrations were measured in 13 pregnant women who gave birth to small-for-date (SFD) infants; this was done during the 3rd trimester of pregnancy. The serum Cu concentration in nonpregnant women was 0.91 +/- 0.19 mg/l. During pregnancy it was significantly higher (1.48 +/- 0.31, 1.91 +/- 0.25 and 2.20 +/- 0.36 mg/l during the 1st, 2nd and 3rd trimesters, respectively) and 5 weeks postpartum it was still higher (1.09 +/- 0.17 mg/l) than in the nonpregnant women. In the cross-sectional population, serum Cu and Zn values were of the same magnitude as in the longitudinal study. When longitudinal and cross-sectional values of serum Cu during the 3rd trimester were combined, the mean level (2.23 +/- 0.40 mg/l) was significantly higher than that in the SFD group (2.06 +/- 0.25 mg/l). Serum Zn in the SFD group (0.48 +/- 0.12 mg/l) did not differ significantly from the normal pregnant values.     

Placental Transfer and Pharmacokinetics of Atropine after a Single Maternal Intravenous and Intramuscular Administration

The placental transfer and pharmacokinetics of atropine were studied in 44 healthy parturients undergoing caesarean section. The concentrations in the plasma were determined by a new radioimmunoassay after intravenous (n = 32) or after intramuscular (n = 12) administration of 0.01 mg/kg of atropine. A fast placental transfer with apparent foetal uptake of the drug was found after intravenous injection. There was also a difference in the umbilical vein and artery concentrations after intramuscular administration. The maternal pharmacokinetics of i.v. atropine obeyed a two-compartment open model with a fast distribution phase (mean tα_1/2 = 1.02 min) and quite fast elimination (t_1/2 = 2.56 h). The total apparent volume of distribution was 1.0 1/kg and the total plasma clearance 6.36 ml/min/kg. The mean peak maternal plasma levels after i.m. atropine administration were found at 1.59 h and the mean calculated half-life of elimination was then 2.1 h. No atropine was found in the amniotic fluid.     

Maternal and fetal plasma renin activity during ritodrine infusion to the mother.

The effect of ritodrine to the mother on plasma renin activity (PRA) in the mother and fetus was examined in 10 mothers coming to elective cesarean section. 10 comparable mothers without ritodrine infusion served as controls. At the end of 2 h infusion of ritodrine, the mean maternal PRA was significantly (p less than 0.001) higher than in the control group. Also the mean PRA levels in the umbilical vein (p less than 0.001) and umbilical artery (p less than 0.01) were significantly higher after ridodrine infusion to the mother than the respective levels in the control group.     

Multicentre study of effects of Org OD 14 on endometrium, vaginal cytology and cervical mucus in post-menopausal and oophorectomized women

A multicentre study covering 69 post-menopausal or oophorectomized women was performed to determine whether Org OD 14 ((7, 17)-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one) administered orally in a daily dose of 2.5 mg for 90 consecutive days induces endometrial proliferation. The treatment with Org OD 14 was continued in combination with 1 mg/day of lynestrenol from day 91 for 10 days to ascertain whether secretory transformation of the endometrium and subsequent withdrawal bleeding would occur. Endometrial biopsies were obtained before treatment and on day 91. The effects of Org OD 14 on vaginal mucosa and cervical mucus were also evaluated.

Org OD 14 did not display any effect on the endometrium in 56 of the study subjects (83.5%). Weak stimulation (initial proliferation) was seen in 11 of the subjects (16.4%) and withdrawal bleeding occurred in only 5 of these after cessation of the combined treatment with lynestrenol. However, moderate ‘oestrogenic’ effects on vaginal mucosa and cervical mucus were induced in all study subjects.     

Effects of pharmacological modulation of the ATP-sensitive potassium channels on the development of warm-up angina pectoris

The aim of this study was to examine the effect of pharmacological modulation of the ATP-sensitive potassium channels in the development of warm-up angina pectoris. Thirty-one patients with stable angina pectoris, a positive exercise test and angiographically documented coronary artery disease underwent three exercise tests 90 min after receiving either glibenclamide 10.5 mg (an ATP-sensitive potassium channel blocker), pinacidil 25 mg (an ATP-sensitive potassium channel opener) or placebo in a blinded fashion. There was a 30-min recovery period between the first and the second test and 60 min between the second and the third test. The rate-pressure product at 1-mm ST-segment depression (ischemic threshold) and the maximum ST-segment depression (STD) adjusted to the highest rate-pressure product common to the three tests were analyzed. In the placebo group, there was a significant increase in the ischemic threshold during the second and third test and a significant decrease in the maximum adjusted STD during the second test which was lost during the third test. This apparent adaptation to exercise-induced ischemia was not seen in the glibenclamide-treated patients. In the pinacidil-treated patients, there was a paradoxical decrease in ischemic threshold during the second test with no change in maximum adjusted STD which tended to be lower than in the placebo-treated patients on each exercise test. This study confirms that the warm-up phenomenon can be induced during repeated exercise testing. The blockade of this phenomenon by glibenclamide suggests that the ATP-sensitive potassium channels may be involved in this potential protective mechanism. At the same time, the paradoxical response in the pinacidil-treated patients flags a warning that drugs acting on the sarcolemmal ATP-sensitive potassium channels may have a direct effect on the ST-segment that may interfere with the interpretation of the electrocardiogram.     

VEGF overexpression improves mesenchymal stem cell sheet transplantation therapy for acute myocardial infarction

Cell sheet‐based tissue engineering shows great potential in the treatment of ischaemic heart disease. However, treatment efficacy is compromised by low blood and nutrient supply. The aim of this study was to investigate the effect of pro‐angiogenic vascular endothelial growth factor (VEGF)‐modified mesenchymal stem cell (MSC) sheet transplantation therapy in ischaemic heart failure. Rat MSCs were manipulated to overexpress the VEGF gene. In vitro, the antiapoptotic and paracrine effects were assessed under hypoxic conditions. In vivo, we evaluated the therapeutic effect of VEGF‐modified MSC sheet therapy in a rat model of acute myocardial infarction (AMI). Forty‐five Wistar rats were divided into three groups; one group underwent AMI (control), another underwent AMI and WT sheet transplantation (WT‐MSC) and a third group underwent AMI and VEGF sheet transplantation (VEGF‐MSC). Echocardiography was performed after 3, 10 and 28 days. Samples for histological analysis were collected at the end of the study. The VEGF gene protected MSCs against apoptosis. In vitro, VEGF overexpression significantly reduced MSC apoptosis compared with wild‐type and enhanced VEGF secretion under hypoxic conditions. Capillary density in the infarct border zone was higher in VEGF‐MSC‐transplanted animals than in WT‐MSC‐treated animals. Furthermore, VEGF‐MSC‐transplanted animals had a smaller infarct size than WT‐MSC‐treated animals and exhibited remarkable functional recovery. These findings support the premise that transplantation of proangiogenic gene‐modified MSCs may be valuable for mediating substantial functional recovery after AMI. Copyright © 2012 John Wiley & Sons, Ltd.     

Midbrain serotonin and striatum dopamine transporter binding in double depression: a one-year follow-up study

Data on neurobiological differences between major depression (MD) and double depression (DD) are scarce. We examined the striatum dopamine (DAT) and midbrain serotonin transporter (SERT) binding of [¹²³I] nor-β-CIT in DD patients (n = 8) and compared it to that in MD patients (n = 11) and healthy controls (n = 19). Drug-naïve patients and controls were imaged by single-photon emission computed tomography at baseline, and the patients also after one year of psychodynamic psychotherapy. Both DD and MD groups had lower midbrain [¹²³I] nor-β-CIT binding compared with the controls. Baseline 17-item Hamilton Depression Rating Scale (HAM-D-17) scores significantly decreased in both groups after one year of psychotherapy (DD: t = 3.55, p = 0.009; MD: t = 5.86, p < 0.001). No differences between the DD and MD groups were observed in age-adjusted baseline striatum or midbrain [¹²³I] nor-β-CIT binding or its change during psychotherapy. Age-adjusted baseline striatum [¹²³I] nor-β-CIT binding correlated inversely with the duration of both dysthymia (rho = −0.76, p = 0.03) and MD (rho = −0.83, p = 0.01) in the DD group. No such finding was observed in the MD group (rho = 0.26, p = 0.44). Baseline HAM-D-17 did not correlate with the change in striatum or midbrain [¹²³I] nor-β-CIT binding in either group. In conclusion, our findings suggest that when using midbrain [¹²³I] nor-β-CIT binding as a marker of SERT binding, no differences are detectable between patients with DD and MD. However, low striatum [¹²³I] nor-β-CIT binding, a marker of DAT binding, may be associated with a longer illness duration in dysthymia.