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The fetal development of the human uterine cervix from the 12th to the 31st postmenstrual week as revealed by scanning electron microscopy. Anatomical and clinical correlations.

To clarify the differentiation of the human uterine cervix, fetuses of the 12th, 15th, 18th, 20th, 21st, 22nd, and 31st postmenstrual week were studied by Scanning Electron Microscopy. At the 12th week the endocervical epithelium consisted of microvillous cells, often showing single cilia and anlages of tubular glands. At the 15th week the cervical canal was entirely formed and its surface cells appeared columnar. At the 18th week these cells were replaced by flat or slightly raised cells, provided with thin microplicae. At the 20th week the endocervical epithelium appeared pseudostratified with higher, apically-convex and shorter basal cells; glands developed in form of tubular invaginations of the luminal epithelium. At the 21st week in the lower part of the endocervix polymorphic, globose cells with short and stubby microvilli and others elongated, having short microplicae, were observed. These latter likely corresponded to the so-called columnar cells undergoing squamous metaplasia. Among microvillous and/or metaplastic cells, a number of apoptotic cells, as globose elements with a ruffled and invaginated surface, were also noted. At the 22nd week evident plicae palmatae were found, covered by microvillous secreting cells. These showed smooth bulged apices releasing droplets by a "micro-apocrine" mechanism. These features increased at the 31st week, when many droplets were noted also around the mouth of the cervical glands. Only at this phase of development fully ciliated cells were found often contacting secretory material. Mature squamous exfoliating cells with complex microplicae covered an hypertrophied portio vaginalis. The squamous cells extended toward a squamo-columnar junction in form of flat, tongue-like projections. Their tips consisted of immature squamous metaplastic cells, which were endocervical columnar progressively becoming elongated elements, exhibiting short microvilli. The above features are rather similar to those occurring during the adult reproductive age. Therefore, it might be hypothesized that, during pregnancy, a common gestational hormonal background may induce somewhat similar morpho-dynamic processes in the cells and tissues of the fetal reproductive tract mimicking what occurs in the adult female.

Cervix Uteri↗

The thyroid-system function in preterm infants of postmenstrual ages of 31 weeks or less: evidence for a "transient lazy thyroid system".

A prospective study was conducted in order to evaluate thyroid function in 20 healthy and 18 sick preterm infants with postmenstrual ages of 31 weeks or less. The clinical condition of both groups was compared using a "Neonatal Special Care Evolution Score". The effect of thyroid hormone treatment, given from D10 on to the sick infants, was also studied. TSH, thyroid hormone levels (TG, T4, T3, rT3, FT4 and FT3) and TBG were measured by radioimmunoassays at D0, D10, D20, D30 and D40. Healthy preterm infants on D0 have a median TSH level of 22 microU/ml and a high TG level of 200 ng/ml; thereafter, median serum levels decrease to 6 microU/ml and 35 ng/ml respectively. During the same period, median serum T4 is maintained at a low level of about 6-8 micrograms/dl, median serum T3 gradually increases from 80 ng/dl on D0 to 150 ng/dl on D40, and median serum rT3 decreases beyond D10 from a plateau of 200 ng/dl to about 100 ng/dl. In the sick preterm infants before treatment, serum TSH is as in the control group but serum T4, T3 and rT3 on D10 are well below the control values (P = 0.005). In all conditions, there is a significant correlation between serum T4 and FT4, and between serum T3 and FT3. Thyroxine, given to the sick preterm infants from D10 on, brings median serum T4 values closely to the ones of the control group whereas serum levels of TSH and TG are unaffected and similar to those of the healthy preterm infants. Furthermore, thyroxine brings serum rT3 within the range of the control group but leaves median serum T3 at a low level of about 50 ng/dl. On T3 treatment, serum T3 normalizes but rT3 and particularly T4 tend to decline further. In the conditions of this study a significant difference in TBG level is not proven. Although an untreated sick group was not enrolled in the study, thyroid hormone treatment brought the "Neonatal Special Care Evolution Score" of the treated sick infants closer to that of the healthy preterm infants. In the sick preterm infant with failure to thrive on D10, there is an impaired thyroid discharge of T4 in spite of serum TSH values not different from those of the control group.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

Hypercapneic ventilatory response in patients with panic disorder before and after alprazolam treatment and in pre- and postmenstrual women.

We tested the ventilatory and anxiety response to hypercapneic (CO2) challenge in women with panic disorder as well as in normal women in the premenstrual phase and mid-points of their menstrual cycles. Panic disorder patients were challenged on two occasions, each time while in the premenstrual phase of the menstrual cycle, receiving an open trial of alprazolam through the intervening 8 weeks between tests. This study confirms previous reports indicating increased sensitivity to CO2 in patients with panic disorder and that this sensitivity can be attenuated by treatment. We found a significant decrease in the ventilatory response of panic disorder patients comparing pre- and post-therapy. We also observed that normal females, while in the premenstrual phase of their menstrual cycle, have a heightened anxiety response to CO2 challenge.

Adult↗

Luteal phase treatment of premenstrual dysphoric disorder improves symptoms that continue into the postmenstrual phase.

BACKGROUND: Despite the proven efficacy of luteal phase medication dosing for women with premenstrual dysphoric disorder (PMDD), it is not known whether this approach adequately treats symptoms that linger into the first 2-3 days of the follicular phase, a time when up to one-third of women diagnosed with PMDD report residual symptoms. Furthermore, no previous study has explored whether abruptly stopping medication after 2 weeks of treatment is associated with discontinuation symptoms. METHODS: To evaluate the efficacy of luteal phase medication dosing, symptom data from the Daily Record of Severity of Problems (DRSP) during first few days of menses were compared from two studies with similar designs but different treatment strategies. The first study used continuous dosing of sertraline, 50-150 mg/day, throughout the menstrual cycle, while the second study used intermittent dosing with sertraline, 50-100 mg/day in the 14-16 days prior to onset of menses. To investigate whether abruptly stopping pills led to discontinuation symptoms, DRSP data for the first 5 days after the onset of menses were analyzed in the second (intermittent dosing) study. Symptom scores were compared for subjects who took either sertraline or placebo premenstrually and ceased taking pills at the onset of menses. RESULTS: The baseline (pretreatment) to on-treatment effect sizes were similar for continuous vs. luteal phase dosing on the first day of menses (0.73 vs. 0.89), second day of menses (0.40 vs. 0.55), and third day of menses (0.42 vs. 0.44), respectively. Subjects who abruptly discontinued sertraline had fewer symptoms indicative of withdrawal at Day 3 (p < 0.01) and no difference during Days 4-5 compared to subjects abruptly discontinuing placebo. CONCLUSION: Patients given active medication during the luteal phase demonstrate reductions in DRSP total scores into the first few days of menses regardless of whether active treatment was continuous throughout the menstrual cycle or was discontinued at the onset of menses. This analysis finds no support for discontinuation symptoms following abrupt cessation of sertraline after 2 weeks of treatment for two cycles.

Adult↗

The development of haemodynamics in the extracranial cerebral arteries of healthy preterm and term neonates.

To investigate the development of cerebral haemodynamics in healthy preterm and term newborns, a prospective colour duplex sonography study was performed in 113 neonates at 32 to 42 weeks of postmenstrual age. In the extracranial internal carotid arteries (ICAs) and vertebral arteries (VAs), luminal diameters and angle-corrected flow velocities were measured. Flow volumes and waveform parameters were calculated. There were no side-to-side or gender-related differences for any of the parameters measured. A marked increase of luminal diameters, end-diastolic and time-averaged flow velocities and flow volumes with postmenstrual age was found in both ICA and VA (p </= 0.0001). Peak systolic velocity did not vary with age, thus, leading to a significant decrease of the resistance and pulsatility indices with rising postmenstrual age. Reference data for flow velocities, waveform parameters, luminal diameters and flow volumes of both ICA and VA are provided for different groups of postmenstrual age. In conclusion, the marked increase in cerebral blood flow volume with postmenstrual age is due to a rise in the luminal diameter of extracranial cerebral arteries and a decrease in peripheral vascular resistance.

Blood Flow Velocity↗

Assessment of neurological status in preterm infants in neonatal intensive care and prediction of cerebral palsy.

The purpose of this study was to determine the diagnostic accuracy of a neurological assessment performed before discharge from the nursery to predict cerebral palsy at three years of age in preterm infants. Infants born < 31 weeks gestation between 1992 and 1996 were assessed using the Lacey Assessment of the Preterm Infant (LAPI) prior to discharge. Infants were classified as having no abnormality, possible abnormality, or definite abnormality. At three years of age, the infants had a neurological examination. Infants were stratified into those assessed at < or = 33 weeks postmenstrual age and those assessed at least once > 33 weeks postmenstrual age. Of the 203 infants, 36 were diagnosed with cerebral palsy at three years. Seven were assessed < or = 33 postmenstrual age and 29 were assessed > 33 weeks postmenstrual age. For infants assessed < or = 33 weeks and classified as having any abnormality (possible or definite), the LAPI had 86% sensitivity, 83% specificity, and 96% negative predictive value for subsequent cerebral palsy. The LAPI was less accurate when applied to infants < 33 weeks postmenstrual age. The LAPI is an accurate diagnostic tool in the preterm period for the prediction of normal motor development or cerebral palsy at three years of age. This information may be used to target intervention.

Cerebral Palsy↗

Efficacy of automated auditory brainstem response hearing screening in very preterm newborns.

OBJECTIVE: To investigate the efficacy of an automated auditory brainstem response (AABR) hearing screening method in very preterm newborns in the neonatal intensive care setting. STUDY DESIGN: In this prospective cohort study, 90 consecutive preterm newborns (<32 weeks' gestational age) had AABR hearing screening weekly from birth until a bilateral pass result was obtained. If the newborn had a unilateral pass result, AABR screening was repeated in the same week. Data were analyzed by using the Kaplan-Meier survival function technique, resulting in a cumulative pass rate curve for postmenstrual age. Cox's regression method was used to analyze the effect of co-variables, such as sex and growth restriction, on pass rates. RESULTS: Median gestational age was 29.5 weeks (range, 25.3-31.9 weeks), and median birth weight was 1115 g (range, 600-1960 g). Mean age was 6.2 days (SD 4.3) at first test, 15.7 (SD 8.1) at second test, and 21.4 (SD 8.6) at third test. Eighty percent (CI: 70.2%-89.8%) of the newborns passed at 30.3 weeks' postmenstrual age, 90% (CI: 83.6%-96.4%) passed at 31.2 weeks, and 100% passed at 34 weeks' postmenstrual age. The attainment of these pass rates correlated to postmenstrual age was not significantly influenced by sex, growth restriction, or gestational age at birth. Postnatal pass rates (in days) were strongly influenced by gestational age. CONCLUSION: AABR pass rates of >80% can be obtained from 30 weeks' postmenstrual age. Therefore AABR neonatal hearing screening can be used before discharge from a neonatal intensive care unit.

Brain Stem↗

Changes in nutrient intake during the menstrual cycle of overweight women with premenstrual syndrome.

This study presents the nutrient data collected from women who were being screened for premenstrual syndrome (PMS) for entry into an intervention study. Screening was by the Steiner self-rated questionnaire. One hundred and forty-four overweight women completed the screening process and eighty-eight met the criteria for PMS. All women kept 4 d diet diaries pre- and postmenstrually over two menstrual cycles. The mean energy and macronutrient intakes were compared between the pre- and postmenstrual phases. Energy and macronutrient intake was also calculated according to food categories. Goldberg's cut-off limit for the ratio of energy intake to estimated basal metabolic rate was used to exclude data that was incompatible with predicted energy requirements. The diet diaries were also used to determine the mean number of meals or snacks eaten pre- and postmenstrually. Nutrient analysis of the diet diaries of the women with PMS showed a significant increase (P < 0.001) in total energy and all macronutrients premenstrually when compared to nutrient intake postmenstrually. Women who did not meet the criteria for PMS showed a significant increase in energy and fat intake (P < 0.05) but not in the other macronutrients. When adjusted for energy, data collected from women with PMS showed a premenstrual significant increase in fat, carbohydrate (P < 0.05) and simple sugars (P < 0.001). There was a significant decrease (P < 0.001) in protein premenstrually. Women not meeting the PMS criteria showed no significant difference between pre- and postmenstrual intakes when adjusted for energy. Analysis according to food categories in women with PMS showed a significantly greater intake premenstrually of energy and all macronutrients for cereals, cakes and desserts and high-sugar foods (P < 0.001). In women with PMS there was a significantly greater number of 'episodes of eating' premenstrually (P < 0.001). This study provides further evidence, to support the very limited number of earlier studies, that there is a group of women with PMS who increase their nutrient intake during the premenstrual phase. This could potentially be a contributing factor for some women experiencing difficulties adhering to suggested dietary modification and should be considered when counselling premenopausal women.

Adult↗

Sleep architecture in term and preterm infants beyond the neonatal period: the influence of gestational age, steroids, and ventilatory support.

STUDY OBJECTIVE: To examine (1) sleep architecture of infants at varied risk for sudden infant death syndrome, (2) delays or advances in preterm infants at term postmenstrual age, (3) whether ventilatory support and gestational age alter sleep, (4) whether steroids alter sleep, (5) confounding influences of sex, small for gestational age, and maternal smoking. DESIGN: Overnight polysomnography. DEPENDENT VARIABLES: Percentage of active sleep, quiet sleep, indeterminate, and awake time per total recording time; mean and longest duration of state epochs; number of episodes > or = 10 minutes; and sleep efficiency. SETTING: Collaborative Home Infant Monitoring Evaluation (CHIME). PARTICIPANTS: Two hundred one preterm and 198 term infants between 33 and 58 weeks postmenstrual age during polysomnography. Fifty-one term infants with an apparent life-threatening event without known etiology (apnea of infancy), 59 subsequent siblings of babies who died of sudden infant death syndrome, and 88 healthy term infants. RESULTS: Tracings of infants with apnea of infancy and healthy term infants were similar. Subsequent siblings of babies who died of sudden infant death syndrome spent less time in quiet sleep. Preterm infants (< or = 37 weeks postmenstrual age) exhibited immature architecture compared with infants of term postmenstrual age. The latter exhibited similar sleep except that they had a lower percentage of quiet sleep and longer mean indeterminate and longest indeterminate episodes. Preterm infants with the youngest gestational age lagged behind older preterm infants. Neither sex nor use of steroids affected sleep. Assisted ventilation was associated with a delay in maturation, small-for-gestational age status with increased active sleep, and smoking with increased awake time. CONCLUSION: With few exceptions, asymptomatic premature infants do not exhibit significant delays in sleep architecture compared with term infants at comparable postmenstrual age. The preterm infant with an early gestational age and morbidity exhibited delayed sleep architecture.

Anti-Inflammatory Agents↗

The development of visual function in normal and neurologically abnormal preterm and fullterm infants.

Pattern preference for four different pairs of patterns, and visual acuity based on the ability to distinguish black and white stripes of different widths, were compared in neurologically normal and abnormal preterm infants at 36 and 40 weeks postmenstrual age and in normal and abnormal fullterm infants in the newborn period and again at four and six weeks of age. The study aimed to chart the maturation process of these visual functions in the neonatal period and to assess their predictive value in the neurologically abnormal infant. Part I of the study deals with the normal infant and Part II with the abnormal infant. In Part I, the maturation process for both visual functions in newborn preterm infants of increasing gestational age is compared with longitudinal assessment of postnatal maturation of these functions in preterm infants up to 40 weeks postmenstrual age. Up to 36 weeks postmenstrual age the functions were comparable in the maturing preterm infants and the newborn infants of comparable postmenstrual age, but at 40 weeks the preterm infants did less well than the fullterm newborn infants. In Part II, the abnormal fullterm infants demonstrated a significantly poorer pattern preference at the initial and subsequent examination. Visual acuity was significantly poorer at the initial examination but less marked at follow-up. The abnormal preterm infants showed poorer pattern preference and visual acuity at both 36 and 40 weeks postmenstrual age. Compared with neurologically abnormal infants without intraventricular haemorrhage (IVH), preterm infants with IVH showed no significant difference in pattern preference at 36 and 40 weeks, but a significant deficit in visual acuity.

Cerebral Hemorrhage↗

Postnatal serum insulin-like growth factor I deficiency is associated with retinopathy of prematurity and other complications of premature birth.

OBJECTIVE: Insulin-like growth factor I (IGF-I) is necessary for normal development of retinal blood vessels in mice and humans. Because retinopathy of prematurity (ROP) is initiated by abnormal postnatal retinal development, we hypothesized that prolonged low IGF-I in premature infants might be a risk factor for ROP. DESIGN: We conducted a prospective, longitudinal study measuring serum IGF-I concentrations weekly in 84 premature infants from birth (postmenstrual ages: 24-32 weeks) until discharge from the hospital. Infants were evaluated for ROP and other morbidity of prematurity: bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), and necrotizing enterocolitis (NEC). RESULTS: Low serum IGF-I values correlated with later development of ROP. The mean IGF-I +/- SEM level during postmenstrual ages 30-33 weeks was lowest with severe ROP (25 +/- 2.41 micro g/L), 29 +/- 1.76 micro g/L with moderate ROP, and 33 +/- 1.72 micro g/L with no ROP. The duration of low IGF-I also correlated strongly with the severity of ROP. The interval from birth until serum IGF-I levels reached >33 micro g/L was 23 +/- 2.6 days for no ROP, 44 +/- 4.8 days for moderate ROP, and 52 +/- 7.5 days for severe ROP. Each adjusted stepwise increase of 5 micro g/L in mean IGF-I during postmenstrual ages 30 to 33 weeks decreased the risk of proliferative ROP by 45%. Other complications (NEC, BPD, IVH) were correlated with ROP and with low IGF-I levels. The relative risk for any morbidity (ROP, BPD, IVH, or NEC) was increased 2.2-fold (95% confidence interval: 1.41-3.43) if IGF-I was <or=33 micro g/L at 33 weeks' postmenstrual age. CONCLUSIONS: These results indicate that persistent low serum concentrations of IGF-I after premature birth are associated with later development of ROP and other complications of prematurity. IGF-I is at least as strong a determinant of risk for ROP as postmenstrual age at birth and birth weight.

Birth Weight↗

Postnatal head growth deficit among premature infants parallels retinopathy of prematurity and insulin-like growth factor-1 deficit.

BACKGROUND: We hypothesized that in premature infants, retinal vascular growth retardation between birth and postmenstrual age of approximately 30 to 32 weeks that initiates retinopathy of prematurity is paralleled by brain growth retardation. METHODS: In a prospective longitudinal study, we measured postnatal head growth, retinopathy of prematurity stage, protein and energy intake, severity of illness and serum insulin-like growth factor-1 levels in 58 preterm infants (mean gestational age at birth: 27.6 weeks) from birth until postmenstrual age of approximately 40 weeks. RESULTS: Premature infant head growth decelerates dramatically after birth until postmenstrual age of approximately 30 weeks. Head growth retardation coincides with retinal vascular growth suppression. Accelerated growth follows between post menstrual ages of approximately 30 to 32 weeks and approximately 40 weeks. The degree of head growth retardation up to postmenstrual age of 31 weeks corresponds to the degree of retinopathy of prematurity and to the degree of suppression of serum levels of insulin-like growth factor-1. At postmenstrual age of 31 weeks, if a child's head circumference SD is below -2.5, then the probability of also developing at least stage 3 retinopathy of prematurity increases fivefold compared with head circumference above -2.5 SD (32% vs 6%) suggesting parallel processes in brain and retina. Serum insulin-like growth factor-1 levels correlate positively with head circumference SD score and with the degree of retinopathy of prematurity. CONCLUSIONS: The correlation between head and retinal growth is consistent with insulin growth factor-1 being one of the postnatal growth factors involved in this multifactorial process and also suggests that factors that contribute to retinopathy of prematurity during this critical period may also affect neurological dysfunction. Additional studies are required to establish this connection.

Female↗