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Several peptide hormones and growth factors have been found in human milk, and we present here the results of measurements of parathyroid hormone-related peptide (PTHrP). A radioimmunoassay (RIA) using a polyclonal antiserum against the mid-region of the molecule has been developed. In milk collected during the first 6 days after parturition, the PTHrP concentrations showed large interindividual variations ranging from 0.3 to 13.7 nmol-Eq/L (0.5 to 24.4 ng-Eq/mL) (n = 67) and increased between days 3 and five postpartum. PTHrP also increased during the first 4 collecting days when measured in milk from the same mother during a prolonged period. On fast-protein liquid chromatography (FPLC), the bulk of PTHrP eluted with a molecular weight of approximately 10 to 12 kd after treatment with urea. After mid-molecule immunoaffinity extraction of PTHrP from milk, higher levels were obtained by the mid-molecule RIA than by an aminoterminal assay, indicating that all fragments did not contain the aminoterminal. Parts of immunoextracted milk PTHrP stimulated cyclic adenosine monophosphate (cAMP) production in rat osteosarcoma cell line, UMR-106. In conclusion, we have found PTHrP-like immunoreactivity in human milk using a mid-region RIA. Parts of the immunoextracts also contained the aminoterminal and possessed PTH-like bioactivity. Whether PTHrP in human milk plays a physiological role in the maternal breast or in the newborn gastrointestinal tract is unknown, but the present observations demonstrate that a portion of the PTHrP is at least potentially biologically active.
Children born small for gestational age (SGA) and children having very low birth weight, less than 1500 g, are claimed to be at risk of developmental problems, even when obvious pathology and disability are absent. In this study, sensorimotor and cognitive development of 14 medically healthy, very-low-birth-weight and small-for-gestational-age children were investigated. The children were born at the Karolinska Hospital between 1979 and 1981. At the time of the assessment, the children were aged 8.7-11.2 years. The assessment instruments included the Wechsler Intelligence Scale for Children, a modified version of the Bruininks-Oseretsky Test of Motor Proficiency, as well as selected subtests from the Halstead-Reitan Neuropsychological Battery and from the Southern California Tests of Sensory Integration. Information was also obtained from obstetric, neonatal and pediatric records, which included early developmental assessments. As a control group, 14 children were recruited and matched for age, sex and socio-economic background. The very-low-birth-weight-small-for-gestational-age group scored significantly lower on measures of visuospatial ability, non-verbal reasoning, strategy formation and gross-motor coordination. The group differences were largely attributable to the subnormal performance of eight of the very-low-birth-weight-small-for-gestational-age children. These children, who also tended to be born earliest (less than 33 weeks), had a high incidence of behavioral and educational problems. These findings are consistent with the view that the very preterm infant develops a different neurobehavioral organization than a full-term infant. Developmental deficits may become increasingly evident in the early school years.
To maintain a closed system during the preparation of blood components, including the removal of buffy coat, many centers use a quadruple blood bag additive solution system which in this study has been reduced to a cheaper triple bag system. The buffy coat and plasma were after centrifugation transferred to the first satellite bag and, after a second spin, the plasma separated from the buffy coat was transferred to the second satellite bag and stored for a fortnight at 4 degrees C. This resulted in a statistically significant increase in platelet factor 4 and elastase activity levels. No significant changes were found in the levels of C1-esterase inhibitor and kallikrein inhibiting activity, thrombin-antithrombin complexes, soluble fibrin, fibrinopeptide A and spontaneous proteolytic activity. The changes observed must be regarded as clinically insignificant. The platelet count is low enough to meet the requirements for platelet poor plasma. Using this blood component separation technique, one can reduce the CPD/additive solution 4-pack blood bag system to a less expensive 3-pack blood bag system.
Cell-poor plasma was prepared by apheresis from 10 donors. From each donor, an amount of 200 ml was frozen rapidly to -40 degrees C in standard blood bags, and a further 200 ml was frozen slowly to -20 degrees C. Before freezing and after thawing, plasma samples were collected and frozen to -70 degrees C pending analysis. Coagulation factor VIII activity was reduced to 90% by rapid freezing and to 80% by slow freezing. Factor V was not influenced by rapid freezing, but slow freezing reduced the levels to 92% of the pre-freezing levels. In some of the plasma bags a slight increase in fibrinopeptide A occurred. However, soluble fibrin, thrombin-antithrombin complexes and spontaneous proteolytic activity were not altered by freezing. The beta-thromboglobulin increased slightly with slow freezing. Moreover, in a separate experiment, evaluating the possible effects of refreezing plasma samples, an increase in beta-thromboglobulin was also recorded, while the levels of factors VIII and V and von Willebrand factor were not affected. The changes in some variables, which were recorded in the cell-poor plasma, frozen soon after the blood donation at a slow freezing rate, must be regarded as insignificant in most clinical situations.
Blood coagulation and fibrinolytic inhibitors and the balance between and within the two systems were investigated in 26 normal pregnant women during pregnancy and the puerperium. The concentration of the coagulation inhibitors antithrombin and protein C remained within normal levels, whereas the mean level of free protein S showed a significant decrease from 0.26 U/mL in early pregnancy to 0.14 U/mL in week 35. At the same time, soluble fibrin levels increased from 9.2 to 13.4 nmol/L and thrombin-antithrombin complexes increased from 3.1 to 7.1 micrograms/L; both are indicators of thrombin activity. A concurrent increase in the levels of the fibrinolytic inhibitors plasminogen activator inhibitor-1 and -2 from 7.4 to 37.8 AU/mL and 31 to 160 micrograms/L, respectively, suggests a decrease in fibrinolytic activity. However, the levels of fibrin D-dimer, ie, fibrin split products, also increased in parallel from 91 to 198 micrograms/L, suggesting that fibrinolysis is present. Thus, a balance normally exists, which is probably why thrombotic events are rare during pregnancy.
The present study was based on data from a longitudinal research program. The cohort consisted of 12,079 children, born in the Stockholm area in 1953. There were 494 children born with low birth weight (LBW; 2500 g or less). The results of the present study showed, that the LBW children had significantly lower school marks and intelligence-test scores (numerical, verbal and logical abilities) at the age of 13 than the normal birth weight children (NBW). For girls reared in non-manual socio-economic status (SES), decreased school marks and IQ-test scores were related to birth weight, and this was especially pronounced for LBW girls born after pregnancy week 37. For boys, however, no decreased school marks and IQ-test scores were related to birth weight and gestational age, with the exception of verbal ability for LBW boys born after pregnancy week 37 reared in non-manual SES.
In 15 women investigated during the follicular, ovulatory and luteal phases of the menstrual cycle, only small variations in plasma levels of oxytocin were found. There was no mid-cycle surge in oxytocin levels. A parallel variation in oxytocin and oestradiol levels was found in five of the women. In 10 women examined every 4th week during gestation starting at week 12, a small but significant increase in oxytocin levels was found. Pronounced fluctuations in oxytocin levels were observed in four of the pregnant women. These fluctuations were independent of the stage of gestation and were also observed in three of the menstruating women. Seven out of 12 women treated with human menopausal gonadotrophin exhibited a marked elevation of oestradiol levels; oxytocin levels also increased and were significantly elevated when the oestradiol level exceeded 2 pmol/ml. Oxytocin levels were higher in the pregnant and human menopausal gonadotrophin-treated women than in the menstruating women. The oxytocin levels appeared to be only partly related to the oestradiol level. It is possible that the stimulatory effect of oestradiol is antagonized by a concomitantly high progesterone level. Alternatively, there may not be a linear dose-effect relationship between oestradiol and the release of oxytocin.
The cohort in the present longitudinal research program consisted of 873 children in an entire school grade, in a Swedish community. The present results showed a main effect of birth weight; low birth weight (LBW) children had lower school performance and intelligence-test (IQ) scores at age 13 than did normal birth weight (NBW) children irrespective of parental SES. Second, there was no significant main effect of gestational age (GA) on scholastic performance and IQ-test scores. Third, there was a significant main effect of the combination of birth weight and GA on scholastic performance and IQ-test scores. The LBW children born at term (38-40 pregnancy weeks; pw) had significantly lower scores and school grades as compared to the control group while the LBW children born with short gestational age (34-37 pw) and with very short gestational age (less than 34 pw) had significantly lower scores and marks in fewer areas of academic attainment.
Growth hormone (GH), placental lactogen (PL), prolactin (PRL), insulin-like growth factor I (IGF-I) and IGF binding protein-1 (IGFBP-1) were determined in serum by radioimmunoassays (RIAs) in 12 women during pregnancy. GH and PL were analyzed by two monoclonal antibodies (Mab 3 and Mab 1) raised against pituitary GH. Serum IGFBP-1 had reached maximum levels at midpregnancy while PRL, PL and IGF-I increased continuously during pregnancy. Mab 1, which cross-reacts with PL, measured consistently higher levels of PL in serum than a commercial PL RIA (p less than 0.01) due to interference of cross-reacting serum proteins in the Mab 1 RIA. The GH-specific Mab 3 showed decreasing GH levels in unfractionated serum throughout gestation, but detected GH-immunoreactive proteins of approximately 40-200 kD after molecular sieve chromatography of pooled serum from late pregnancy. It is suggested that the formation of GH complexes of large molecular mass account for the successive disappearance of monomeric GH during pregnancy.
The subjects (N = 50) were born to mothers who had earlier participated in an extensive clinical investigation during their pregnancies. Maternal serum hormone levels were investigated from pregnancy week 20 and on to partus. Fourteen children were born small-for-gestational age (SGA) and eight pre-term appropriate-for-gestational age (AGA). Each SGA child had two control children, born to mothers with normal or high serum levels of alpha-fetoprotein (AFP) in pregnancy week 16-17. Elevated serum levels of AFP was considered to be a sign of fetal stress. All 50 children were administered the WISC-test at 10 years of age. The SGA children had lower scores than control children in Performance and Full scale scores. The pre-term SGA children had lower scores than the controls in Verbal, Performance and Full scales. That was not the case for on-time SGA and pre-term AGA children. Girls born to smoking mothers performed less well than girls of non-smoking mothers on the Verbal scale. Positive correlations of maternal serum hormone levels (oestriol, hCG, and hPL) and WISC-test scores were present for girls. For boys a single maternal hormone in pregnancy (prolactin) was correlated with WISC-test scores at 10 years of age.
A total of 222 pregnant women had repeated hormone assays between 20 weeks and delivery; 86 of the women were smokers. The maternal hormone balance appeared to be affected by smoking. Smoking affected maternal serum levels of hPL and hCG in pregnancies with a female fetus whereas maternal serum concentrations of oestriol and prolactin were affected in pregnancies with a male fetus. Significantly higher hCG levels were found in mothers who smoked and had a girl than in those who smoked and had a boy. On the basis of our results we feel that smoking mainly affects the placenta.
A total of 222 pregnant women had repeated hormone assays of prolactin, estriol, human chorionic gonadotrophin and placental lactogen between week 20 and delivery. The aim of this study was to investigate whether maternal serum levels of the above-mentioned hormones differed between normal and abnormal pregnancies, that is preterm, preterm small-for-date (SFD), SFD at-term and normal at-term deliveries, with special regard to fetal sex. The results of the present study indicated differences related to preterm deliveries and intrauterine growth retardation. This finding was reflected in the estriol levels when mothers of both boys and girls were included, suggesting a primary involvement of fetoplacental factors in these pathological pregnancies. However, when only mothers of girls were investigated, the development of growth retardation was mainly seen in maternal serum hPL differences, thus suggesting a placental involvement.
This study was based on data from a longitudinal research program. The cohort consisted of 874 normal children in an entire school grade in a Swedish community. The aim of the study was to investigate the relation between birth weight and behavior at school, for all children and for each sex separately. The results identified specific aspects of behaviour disorder significantly related to low birth weight (LBW) for children at the age of 10 but not at the age of 13. When the sexes were separated, there were no relations between birth weight and deviant behaviour for boys of low birth weight as compared to boys of normal birth weight, while girls of low birth weight showed specific behavioural disorders at age 10 as compared to girls of normal birth weight. For girls reared in families of low parental socioeconomic status, aggressiveness and motor restlessness at age 10 but not at age 13 was also present. Further analyses showed that girls born small-for-gestational age showed lack of school motivation and concentration difficulties both at age 10 and age 13.
The objective of the present study was to measure plasma levels of cholecystokinin (CCK-8 and CCK-33,39) as well as of gastrin during the menstrual cycle and pregnancy. Cholecystokinin and gastrin levels were measured by radioimmunoassay. Before being assayed for cholecystokinin, plasma samples were submitted to HPLC which allowed separation of gastrin and cholecystokinin as well as between CCK-8 and CCK-33,39. Fasting CCK levels were 5.2 +/- 0.6 and 7.1 +/- 0.9 pM during the follicular and luteal phases of the menstrual cycle, respectively. The difference was significant (P less than 0.05). CCK levels were 8.7 +/- 1.2, 10.1 +/- 1.6 and 10.4 +/- 1.2 pM during the first, second and third trimester, respectively. CCK levels during pregnancy were significantly higher than during the menstrual cycle. The ratio between CCK-33,39 and CCK-8 appeared to increase during pregnancy. Gastrin levels remained unchanged during the menstrual cycle and pregnancy. The role of the high levels of cholecystokinin may be to stimulate the exocrine and endocrine pancreatic function during pregnancy. Furthermore, since cholecystokinin inhibits gastric emptying, it may play a role in the sickness of early pregnancy.
Prostaglandin E2 (PGE2) was administered orally in a dose of 1 mg to healthy males (n = 20) and females (n = 10). Blood levels of 15-keto-13,14-dihydroprostaglandin F2 alpha (PGF2 alpha-M) and 15-keto-13,14-dihydroprostaglandin E2 (PGE2-M), determined as the rearrangement product 11-deoxy-15-keto-13,14-dihydro-11 beta, 16-cycloprostaglandin E2 (PGE2-cyclo-M), were measured. The levels of the two PG metabolites increased already 10 minutes after ingestion of the tablet and the mean peak value for PGE2-cyclo-M in the men was 4.64 nmol/l which was reached 50 minutes after PGE2 administration. The mean peak value in women was 4.99 nmol/l which was obtained after 30 minutes. The increase in PGE2-cyclo-M concentration was significantly faster (p less than 0.05) in women than in the men. The mean plasma concentration of PGF2 alpha in males were 0.20 nmol/l prior to treatment and rose after PGE2 ingestion to mean peak level of 0.84 nmol/l after 70 minutes. The corresponding values for the females were 0.18 nmol/l and 0.88 nmol/l 50 minutes into treatment. When the data from both sexes were amalgamated PGE2-cyclo-M peak levels were reached significantly (p = 0.004) sooner than the PGF2 alpha-M peak. The two PG metabolites returned to baseline levels in 70% of the individuals after 240 minutes. The increase in PGF2 alpha-M concentration following oral administration of PGE2 indicates that part of the PGE2 was reduced to PGF2 alpha.(ABSTRACT TRUNCATED AT 250 WORDS)
A single 1 mg dose of prostaglandin (PG) E2 was given orally to 19 men. Ejaculates were obtained 90 minutes and 24 and 48 hours thereafter. Before treatment, each man delivered another three semen samples with the same time intervals as during the study period. PGE2 was also administered to seven men during naproxen treatment and ejaculates were sampled as above. PGE2 did not influence the 90 minutes' posttreatment ejaculates, but after 24 hours there was a significant (P less than 0.05) decrease in sperm counts as compared to the control samples. The change in sperm count was suggested to be due to an effect of PG on the contractile elements in the deferent duct. Sperm motility, viability, and morphology as well as semen volume and adenosine triphosphate (ATP) content remained unchanged. The total semen PGE content was increased 24 hours after treatment from 169 micrograms/ejaculate to 213 micrograms/ejaculate (P = 0.02). In the combined PGE2/naproxen treatment the PGE levels were significantly (P less than 0.05) elevated in the ejaculate 48 hours after treatment. The increase may indicate an increased de novo synthesis of prostaglandins. Based on the results from the analysis of the composition of the 19-hydroxy PGF-isomers with and without naproxen treatment, it is speculated that oral PGE2 influences the cyclo-oxygenase activity.
120 women with elevated alpha-fetoprotein (AFP) in pregnancy week 16-17 were subsequently supervised every 4th week until a few days postpartum. A group of 102 women with normal (n = 78) or low (n = 24) serum AFP concentrations in pregnancy week 16-17 were studied in the same way. In the last week before parturition the AFP serum level declined and the decrease was more pronounced with increasing gestational duration up to pregnancy week 41. The AFP level relationship between the women was stable on average throughout the pregnancies. Smoking was found to be related to elevated maternal serum AFP levels in pregnancy week 16-17. Among mothers younger than 25 years, 72% of those with high or very high AFP serum levels in pregnancy week 16-17 were smokers. Among women with elevated or much elevated maternal serum AFP levels in pregnancy week 16-17, male fetuses predominated. But only those carrying female fetuses gave premature birth to small-for-date children. Further analysis of the data revealed that if such a woman was a multipara, there was a 54% risk of a small-for-date premature female baby. Other data indicate that this risk may be increased by smoking and maternal age. It is recommended that this category of mothers with elevated AFP in pregnancy week 16-17 is continuously supervised during pregnancy.