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PubMed1990

Host heterogeneity in female breast cancer: possible significance for pathophysiology, therapy, and prevention.

Longitudinal studies on human growth have revealed seasonal patterns in the gain of height in 1/3 of the population. Seasonal sensitivity of growth velocity is apparently linked with a lean body structure. This being so, a subgroup with specific biological features could be isolated, including specific endocrine mechanisms (e.g. shorter interval between menarche and menopause, higher incidence of irregular early postmenstrual cycles, and higher concentration of growth hormone secretion) and specific metabolic pathways (more frequent drinking, smoking, and use of the contraceptive pill). This biological specificity may be responsible for behavioral heterogeneity in cancer in general and in breast malignancies in particular. One third of the breast cancer patient population is hormone responsive. The response to all the methods of cancer adjuvant therapy (including ablation of hormone producing organs, chemotherapy, and immunologic manipulation) used up till now does not surpass 33% in the long run. Breast cancer risk reduction by 1/3 due to full-term teenage pregnancies suggests that this may be a consequence of the interruption of a premalignant process initiated in women of the aforementioned subgroup. Simulation of early pregnancy might therefore lead to prevention of breast cancer in women who had seasonal growth patterns as children.

Adult↗

PubMed1985

Clinical experience with the MLCu250 IUD (eight-year results).

Between 1977 and 1981, 1561 MLCu250 standard model IUDs were inserted at the Family Planning Center, Department of Obstetrics and Gynecology, University Medical School of Debrecen, Hungary. The majority were in the first (61.3%) and second (32.2%) segment and only a few were in the third (5.4%), fourth (1.0%) or fifth (0.1%) segment. Insertions were performed in the postmenstrual, postabortal, postpartal and postpuerperal periods. This report evaluates the data for interval insertions only, representing a total of 1457 cases and 65762 woman-months of use during an 8-year follow-up period. Using Tietze's life table technique, cumulative and yearly specific termination rates have been calculated. Fifty per cent of the devices were in place after 5 years of use, and 27.8% of the patients wore the IUD even at the end of the eighth year after insertion. The pertinent termination rate (pregnancy, expulsion, removal for bleeding/pain and for other medical reasons together) was 56.8 in the 96th ordinal month. These findings prove the good over-all performance of the MLCu250 IUD and demonstrate a longer life span for the device than was previously expected.

Female↗

PubMed1993

Qualitative changes in general movements and their prognostic value in preterm infants.

Qualitative assessments of general movements have been shown to have considerable power in predicting neurological outcomes in preterm infants with brain damage. In the present study such assessments were made in 35 preterm infants without major neurological problems before term age, born between 27 and 34 weeks gestation, of whom 12 were small-for-gestational-age (SGA). Most infants maintained a normal or (mildly) abnormal quality from 35 weeks postmenstrual age through 6, 12, 18 to 24 weeks corrected age. Seven changed from initially abnormal movements to a normal quality, six of them after 12 weeks. Differences between SGA and appropriate-for-gestational-age infants became less evident with age, particularly after 12 weeks. This was not the case when comparisons were made on the basis of gestational ages below or above 32 weeks. The prediction of neurological and mental outcomes at 1 year also improved after 12 weeks, around which age a major transformation in neural functions occurs. It is concluded that assessments of movement quality are particularly successful in predicting abnormal outcomes in comparison to examinations based on muscle tone and elicited responses.

Age Factors↗

PubMed1981

[Head circumference and brain development. Growth retardation during intrauterine malnutrition and catch-up growth mechanisms (author's transl)].

Today the close correlation between head circumference growth and brain development in the last weeks of gestation and in the first two years of life is no longer disputed. A recently developed formula even allows for calculations of brain weight based upon head circumference data. Between the ages of 32 postmenstrual weeks and six months after expected date of delivery there is a period of very rapid brain growth in which the weight of the brain quadruples. During this growth spurt there exists an increased vulnerability by unfavorable environmental conditions, such as malnutrition and psychosocial deprivation. The erroneous belief still being prevalent that the brain of the fetus and young infant is spared by malnutrition, can be looked upon as disproved by new research results. Severe malnutrition during the brain growth spurt is thought to be a very important non-genetic factor influencing the development of the central nervous system (CNS) and therewith intellectual performance. In the past a permanent growth retardation of head circumference and a reduced intellectual capacity usually was observed in small-for-gestational age infants (SGA). Nowadays, however, there can be found also proofs of successful catch-up growth of head circumference and normal intellectual development after early and high-energy postnatal feeding of SGA infants. The development of SGA infants of even very low birth weight can be supported in such a way that it takes a normal course by providing good environmental conditions, such as appropriate nutrition - especially during the early growth period - and a stimulating environment with abundant attention by the mother.

Adolescent↗

PubMed2005

O-demethylation of tramadol in the first months of life.

OBJECTIVE: Assess in vivo O-demethylation activity in the first months of life. METHODS: Time-concentration profiles of tramadol (M) and O-demethyl tramadol (M1) in plasma and urine were simultaneously collected in the first 24 h of continuous intravenous tramadol administration in neonates and young infants. M and M1 were determined by high performance liquid chromatography. Correlations between perinatal characteristics [postnatal age (PNA), postmenstrual age (PMA)] and the contribution of metabolites (M, M1) to overall tramadol elimination and to the plasma and urine log M/M1 were calculated. RESULTS: Plasma samples were available in 20/29 and complete 24-h urine collections were available in 25/29 neonates (25-53 weeks PMA). Mean plasma log M/M1 value (>4 h, n=86) was 0.8 (SD 0.4). A significant correlation between plasma log M/M1 and PMA (r=-0.73, P<0.0001) and PNA (r=-0.58, P<0.005) was observed. In a multiple regression model, only PMA remained an independent variable. Mean urine log M/M1 was 0.94 (SD 0.7). Significant correlations of the urine log M/M1 ratio with PMA (r=-0.73, P<0.0001) and PNA (r=-0.56, P=0.0035) were observed. In a multiple regression model with the urine log M/M1 ratio as dependent variable, only PMA remained an independent variable. The maturational half-life of the log M/M1 ratio in early neonatal life in the age range evaluated is about 12-16 weeks without plateau. CONCLUSIONS: O-demethylation activity was already observed in early neonatal life. A significant correlation with PMA was documented, but PMA can only partially explain the observed variability in O-demethylation activity. Polymorphism therefore likely already contributes to the interindividual variability observed in neonates.

Aging↗

PubMed2006

Magnetic resonance imaging assessment of brain maturation in preterm neonates with punctate white matter lesions.

INTRODUCTION: Early white matter (WM) injury affects brain maturation in preterm infants as revealed by diffusion tensor imaging and volumetric magnetic resonance (MR) imaging at term postmenstrual age (PMA). The aim of the study was to assess quantitatively brain maturation in preterm infants with and without milder forms of WM damage (punctate WM lesions, PWML) using conventional MRI. METHODS: Brain development was quantitatively assessed using a previously validated scoring system (total maturation score, TMS) which utilizes four parameters (progressive myelination and cortical infolding, progressive involution of glial cell migration bands and germinal matrix tissue). PWML were defined as foci of increased signal on T1-weighted images and decreased signal on T2-weighted images with no evidence of cystic degeneration. A group of 22 preterm infants with PWML at term PMA (PWML group) were compared with 22 matched controls with a normal MR appearance. RESULTS: The two groups were comparable concerning gestational age, birth weight and PMA. TMS was significantly lower in the PWML group than in the control group (mean TMS 12.44 +/- 2.31 vs 14.00 +/- 1.44; P = 0.011). Myelination (mean 2.76 +/- 0.42 PWML group vs 3.32 +/- 0.55 control group, P = 0.003) and cortical folding (3.64 +/- 0.79 vs 4.09 +/- 0.43, P = 0.027) appeared to be significantly delayed in babies with PWML. CONCLUSION: Conventional MRI appears able to quantify morphological changes in brain maturation of preterm babies with PWML; delayed myelination and reduced cortical infolding seem to be the most significant aspects.

Brain↗

PubMed2006

Efficacy of Yasmin in premenstrual symptoms.

OBJECTIVE: To evaluate the effect of oral contraception formulation with drospirenone (Yasmin) on premenstrual symptoms. MATERIALS AND METHODS: An open-label non-comparative clinical trial was conducted. One hundred women who desired oral contraception for at least 6 months were recruited. The subjects received a blister pack which contained 21 tablets of 3 mg drospirenone/30 microg ethinyl estradiol for the first four cycles (1 cycle = 28 days). Cycle-5 and -6 blister packs were dispensed during the next visit in cycle 4. The subjects were evaluated on menstruation-related symptoms by using the women's health assessment questionnaire (WHAQ) at baseline and at each follow-up visit for three phases of their menstrual cycle. The measured outcome was the mean score changes from baseline to cycle 6 of WHAQ categories. RESULTS: Of the total 100 subjects, 92 (92%) completed the study. At the premenstrual phase, a significant decrease was seen from baseline to cycle 6 in the mean WHAQ scores for impaired concentration, water retention, negative effect, increased appetite, feeling of well-being and undesirable hair change. At the menstrual phase, a significant decrease was seen from baseline to cycle 6 regarding the mean WHAQ scores for impaired concentration, negative effect, feeling of well-being, and undesirable hair change. At the postmenstrual phase, significant changes were consistently observed regarding the feeling of well-being and undesirable hair change. CONCLUSIONS: Oral contraception formulation with drospirenone (Yasmin) has an ameliorating effect on premenstrual symptoms. This oral contraception may have a role in women who are looking forward to use contraception and also suffer from premenstrual symptoms.

Adult↗

PubMed2007

Analgesia in preterm newborns: the comparative effects of sucrose and glucose.

The aim of this study was to evaluate the effectiveness of different oral carbohydrate solutions for alleviation of pain in healthy preterm babies. Thirty-one preterm infants who were having blood drawn by heel prick were given 2 ml of solution A (20% sucrose), solution B (20% glucose) or solution C (placebo, sterile water) into the mouth, 2 min before lancing. Behavioural responses to this painful stimulus were measured by duration of crying and facial expressions (Neonatal Facial Coding System, NFCS) and physiological responses were measured by heart rate (HR), respiratory rate (RR), and oxygen saturation changes (SaO(2)). Infants had a mean birth weight (+/-SD) of 1,401 g (406), gestational age of 30.5 weeks (2.7); at the time of the procedure the postmenstrual age was 32.3 weeks (1.5). There was no significant difference in the time spent squeezing the heel between the three groups (P = 0.669). After the heel prick of both the sucrose and glucose groups the duration of first cry and total crying time was significantly reduced (P = 0.005 and P = 0.007). When the babies received placebo they showed a significantly higher NFCS score at 4 and 5 min after the heel prick (P = 0.009 and 0.046 respectively). Following painful stimulus HR increased significantly in the first 3 min compared with baseline, and at the first minute the mean of the HR was found to be significantly higher in the placebo group than in the sucrose and glucose groups (P = 0.007). We concluded that both sucrose and glucose administered orally before a heel prick reduce the pain response in preterm infants.

Administration, Oral↗

PubMed1997

Blood transfusion and chronic lung disease in preterm infants.

UNLABELLED: Frequent blood transfusions may produce changes in iron status which can give rise to oxygen-derived free-radical (ODFR) generation and oxidative injury. Preterm infants developing chronic lung disease (CLD) receive significantly more transfusions. A total of 73 very preterm infants had weekly estimations of serum iron, transferrin, transferrin saturation, ferritin, caeruloplasmin, bleomycin detectable ('free') iron (BDI), and thiobarbituric acid reacting substances (TBARS) made over the first 28 days. Thirty infants remained oxygen dependent at 36 weeks postmenstrual age and were termed as having CLD. They were significantly lighter and less mature at birth and received more than twice as many transfusions during the 1st month. They had significantly lower transferrin levels initially but similar total iron and transferrin saturations as non-CLD infants. Ferritin and caeruloplasmin levels rose to significantly higher levels over the 1st month in CLD infants, and ferritin levels were significantly related to the number of transfusions given. Infants with higher ferritin levels were more likely to show BDI, although this was not associated with increased lipid peroxidation as evidenced by higher TBARS. CONCLUSION: It is unlikely that oxidative injury from ODFRs induced by blood transfusion contributes to the risk of developing CLD in preterm infants.

Bronchopulmonary Dysplasia↗

PubMed2003

Renal phosphate handling of premature infants of 23-25 weeks gestational age.

Premature infants with low serum phosphate concentrations (<2 mmol/l) are at risk for osteopenia. Therefore, serum phosphate levels in premature infants should be kept above 2 mmol/l. Premature infants of 26-31 weeks gestational age (GA) have renal phosphate threshold concentrations (Tp/GFR) in the range of normal serum phosphate values (2 mmol/l). Therefore, these infants show significant urinary phosphate excretion only when serum phosphate levels are normal, and urinary phosphate excretion can be used to monitor phosphate supplementation. However, few data are available on extremely premature infants of 23-25 weeks GA. The objective of this study was to compare Tp/GFR levels in infants of 23-25 weeks GA to those in infants of 26-31 weeks GA. We retrospectively evaluated case notes of 12 infants of 23-25 weeks GA and compared them to 19 infants of 26-31 weeks GA. Tp/GFR was calculated from simultaneous measurements of urinary phosphate, urinary creatinine, serum phosphate, and serum creatinine. Tp/GFR values 3-5 weeks postnatally were lower in infants of 23-25 weeks GA (1.06+/-0.36 mmol/l, p<0.001) than in infants of 26-31 weeks GA (1.76+/-0.26 mmol/l). Near term (35-37 weeks postmenstrual age), there was no significant difference between Tp/GFR values in infants of 23-25 weeks GA (1.83+/-0.32 mmol/l) and in infants of 26-31 weeks GA (2.05+/-0.22 mmol/l). We conclude that at 3-5 weeks postnatally, infants of 23-25 weeks GA are at risk for low Tp/GFR values, leading to urinary phosphate excretion even in the presence of low serum phosphate levels. In these infants, serum phosphate levels should be monitored, and phosphate supplementation should be adjusted to keep serum phosphate levels above 2 mmol/l.

Birth Weight↗

PubMed2003

Premenstrual symptomatology, locus of control, anxiety and depression in women with normal menstrual cycles.

The present study was designed to investigate the relationships between premenstrual symptomatology, locus of control, anxiety, and depression in women with normal menstrual cycles. Sixty-nine female participants completed a survey, comprised of the Menstrual Distress Questionnaire (MDQ; Moos, 1968), Levenson's (1981) locus of control scales, the Depression Anxiety Stress Scale (DASS; Lovibond and Lovibond, 1995), and a questionnaire constructed by the researchers based on the DSM-IV criteria for Premenstrual Dysphoric Disorder (PMDD). Both overall and specific subtypes of premenstrual symptomatology were found to correlate with external locus of control, anxiety, and depression. In addition, locus of control was found to moderate the relationship between premenstrual symptomatology, anxiety and depression. Finally, women who were in the premenstrual phase when completing the questionnaire scored significantly lower on the internal scale than those in either the follicular or early luteal phases. It was concluded that an external locus of control may be associated with a susceptibility to depression or anxiety when certain premenstrual or postmenstrual changes are experienced.

Adult↗

PubMedDate not supplied

Cerebral mantle thickness: a measurement useful in anatomic diagnosis of fetal ventriculomegaly.

The ultrasonographic diagnosis of cerebral ventriculomegaly carries grave implications, in that affected fetuses may suffer abnormal postnatal development or therapeutic abortion. It is important for pathologists to corroborate the clinical diagnosis, but because diagnostic methodologies and criteria differ so radically, this can be problematic. The clinical diagnosis is made primarily by serial ultrasound examinations of the cerebral ventricles, spaces that can be altered postmortem, particularly when the brain is autolysed or deformed artifactually. We therefore sought to learn if examination of tissue, rather than spaces, can identify accurately those fetuses diagnosed with cerebral ventriculomegaly by prenatal ultrasound. The thickness of the cerebral mantle was obtained in 100 control fetuses aged 14 to 26 postmenstrual weeks. Statistical analysis revealed significant correlation of cerebral mantle thickness with crown-rump length, foot length, and head circumference. Twenty fetuses diagnosed with ventriculomegaly showed mantle thicknesses that were less than the control mean. In a few cases, mantle thickness fell between the mean and -1 SD; in several others, thickness was diminished by -1 SD to -2 SD; in one-half of cases, mantle thickness was 2 SDs or more below the expected mean. Head circumference was within 2 SDs of the control mean in most cases, and increased beyond 2 SDs in only two cases. Head circumference is an unreliable indicator of ventriculomegaly in the midgestational fetus. By contrast, cerebral mantle thickness is a simple and useful way of corroborating ultrasonographic diagnoses at autopsy and may also prove useful in clinical settings.

Case-Control Studies↗

PubMed2005

The effect of alpha-linolenic acid and linoleic acid on the growth and development of formula-fed infants: a systematic review and meta-analysis of randomized controlled trials.

This systematic review and meta-analysis aimed to evaluate the effect of modifying 18-carbon PUFA [18-C PUFA: alpha-linolenic acid (ALA, 18:3n-3) and linoleic acid (LA, 18:2n-6)] in the diets of term and preterm infants on DHA (22:6n-3) status, growth, and developmental outcomes. Only randomized controlled trials (RCT) involving formula-fed term and preterm infants, in which the 18-C PUFA composition of the formula was changed and growth or developmental outcomes were measured, were included. Differences were presented as control (standard formula) and treatment (18-C PUFA-supplemented formula). Primary analyses for term infants were 4 and 12 mon and for preterm infants 37-42 and 57 wk postmenstrual age. Five RCT involving term infants and three RCT involving preterm infants were included in the systematic review. Infants fed ALA-supplemented formula had significantly higher plasma and erythrocyte phospholipid DHA levels than control infants. There was no effect of ALA supplementation on the growth of preterm infants. In term infants, ALA supplementation was associated with increased weight and length at 12 mon, which was at least 4 mon after the end of dietary intervention. Developmental indices of term infants did not differ between groups. There was a transient improvement in the retinal function of preterm infants fed ALA-supplemented diets compared with controls. The findings suggest that ALA-supplemented diets improve the DHA status of infants. Further studies are needed to provide convincing evidence regarding the effects of ALA supplementation of formula on infant growth and development.

Body Size↗

PubMed1976

Studies on the cytodynamics of human endometrial regeneration. II. Transmission electron microscopy and histochemistry.

The morphologic observations made in this study indicate that postmenstrual endometrial resurfacing occurs by proliferation of epithelial cells originating from the stumps of residual basal glands and uterine surface lining, bordering the denuded areas, respectively. Endometrial stromal cells or glands of the residual spongiosa are not involved in uterine surface repair. The mechanism whereby the new surface develops, it is proposed, is by endomitotic division. This contention is supported by the accelerated nuclear DNA and intracytoplasmic RNA synthesis, and absence of mitosis in the newly formed surface epithelial cells. The results indicate, furthermore, that uterine surface reconstruction, which is completed by cycle day 5, is independent of ovarian hormonal stimuli, whereas further endometrial growth, connective tissue remodeling, and metabolic enzyme synthesis are influenced by the gradual increase of preovulatory estrogens.

Adult↗

PubMed1986

Trend analysis of the symptoms of 150 women with a history of the premenstrual syndrome.

The daily symptom records of 150 untreated women with a convincing history of the premenstrual syndrome were investigated qualitatively and quantitatively by means of time series analysis in the form of Trigg's technique for trends. Symptoms were monitored with use of a modified menstrual distress questionnaire. Analysis showed that, depending on the symptom cluster, 60.7% to 85.3% of the women showed symptom trends consistent with the syndrome, 14.0% to 35.3% had trends not typical of the syndrome, and in 0% to 5.3% of records significant trends were absent. Since over 80% of the women were found to have premenstrual syndrome trends for three or more of the six symptom clusters studied, including 32% who showed this trend pattern for all symptoms, a retrospective history of premenstrual syndrome is likely to be confirmed on prospective assessment for at least some symptoms. Quantitatively women who fulfilled the diagnostic criteria for premenstrual syndrome differed from those who did not by exhibiting significantly greater exacerbation of symptoms premenstrually and lesser morbidity postmenstrually. While water retention, negative affect, and pain were the three symptom clusters associated with the most severe ratings, the majority of women suffered from a mixture of physical, psychological, and behavioral complaints, and it was not possible to subdivide the study group by the type of symptoms.

Adult↗

PubMed1988

Alteration of platelet serotonergic mechanisms and monoamine oxidase activity in premenstrual syndrome.

Platelet uptake and content of 5-hydroxytryptamine (5-HT), platelet monoamine oxidase (MAO) activity, and plasma free and total tryptophan levels were determined in patients diagnosed with premenstrual syndrome (PMS) and in control subjects. The Vmax of 5-HT uptake and 5-HT content in platelets of PMS patients were significantly decreased during the premenstrual phase (cycle days -9 to -1) compared to control subjects. Platelet MAO activity was significantly lower postmenstrually (cycle days 5-9) in PMS patients compared to the premenstrual phase. There were no differences in plasma free and total tryptophan levels between PMS patients and control subjects during either interval. As platelets are believed to be a peripheral model for central serotonergic neurons, the results suggest that PMS symptomatology may be related to alterations in serotonergic neuronal mechanisms.

Adult↗

PubMed1980

Patterns of ovulation and bleeding with a low levonorgestrel-releasing intrauterine device.

Patterns of bleeding and plasma concentrations of levonorgestrel, progesterone, estradiol, LH and FSH were studied in ten volunteers who had a levonorgestrel-releasing IUD inserted postmenstrually. The IUD was designed to release 12 microgram/day. All but two of the volunteers ovulated during treatment. The ovulatory cycles differed from the control cycles by being longer and by having depressed plasma progesterone levels during the luteal phases. Intermenstrual spottings occurred frequently during the first sixty days of treatment. No pregnancies occurred during the course of the study.

Adult↗

PubMed1981

Intrauterine contraception with Nova-T and copper-T-200 during three years.

A randomized comparative trial on the clinical performance of two copper-releasing IUDs (Nova-T and Copper-T-200) was performed simultaneously in Denmark, Finland and Sweden. After three years the cumulative pregnancy rate was 1.9 for Nova-T and 5.0 for Copper-T. This difference in efficacy was statistically significant (p less than 0.001). Copper-T had a lower expulsion rate (p less than 0.05) in the total series but not in postmenstrual insertions. Differences between the two devices in other termination rates were not statistically significant. Analysis according to age and parity demonstrated that the pregnancy rate of Nova-T was lower than that of Copper-T in every age and parity group. The pregnancy rate of Nova-T was not effected by age or parity whereas the pregnancy rate and the expulsion rate of Copper-T decreased with increasing age and parity. The removal rate because of infection decreased markedly after the first year of use for both devices. The cumulative rate of removals for infection during the three years of use was not significantly correlated to age and there was no correlation to parity. The continuation rates increased with age and parity. The continuation rates of nulli- and primiparous women were almost identical with both devices and lower than continuation rates of women with 2 or three or more children. Only 11% of the women were lost to follow-up during 36 months. Nova-T had superior effectiveness in preventing undesired pregnancies when compared with Copper-T. The performance of Nova-T is less affected by age and parity then the performance of Copper-T. The silver core in copper wire gives a prolongation of the life-span for Nova-T. For these reasons, Nova-T appears to meet the requirements for an ideal IUD.

Adult↗