Neurotrophic keratitis.

Neurotrophic keratitis (NK) is a rare degenerative corneal disease that occurs as a result of partial or total impairment of trigeminal innervations, leading to a reduction (hypoesthesia) in or loss (anaesthesia) of corneal sensitivity. The impairment of sensory innervation causes a reduction in the lacrimation reflex and the vitality, metabolism and mitosis of epithelial cells, with subsequent deficiency in epithelial repair, stromal and intracellular oedema, loss of microvilli, and abnormal development of the basal lamina. Several recent studies have proposed different therapies based on different aetiopathogenetic theories. The aim of the therapy is to treat aetiopathogenesis and, at the same time, promote corneal healing. In this paper, we report the aetiology, diagnosis, management, and medical and surgical treatment of NK, also indicating future treatments based on the most recent studies.

The pathogenesis of endometrial polyps: a systematic semi-quantitative review.

UNLABELLED: The pathogenesis and natural history of endometrial polyps are not very clear. The objective of this study was to assess the opinions of international medical literature regarding the factors involved in the pathogenesis of endometrial polyps and to organize the results consistently with what is known about endometrial physiology. MATERIALS AND METHODS: A systematic review was carried out with the following search engines: PubMed, OVID, Scopus, SCIELO, and AJOL. Two hundreds forty-six abstracts were selected from the literature; of these abstracts, 58 factors were extracted and set as causative, non-causative, unclear or protective link with endometrial polyps. This relation is described through a correspondence analysis and tested with a main effect hierarchical log-linear model. RESULTS: The log-linear model resulted significant for the correspondence found with the following factors: (i) causative link (ageing, bcl-2 protein, excess weight/obesity, tamoxifen regardless of timing, relationship between estrogen receptors and prog-estinics, unbalanced estrogen therapy, estrogen-like effect, and unbalance between estrogens and progestinics), (ii) protective link (progestinics, antiestrogenic action), (iii) unclear link (menopause, ki-67 protein, angiogenesis, tamoxifen for a short time, tamoxifen for a long time, hormone replacement therapy (HRT), endometritis/inflammation), and (iv) non-causative link (none of the factors specifically). DISCUSSION: Subsequently to a review of the physiology of the endometrium, the onsetting of endometrial polyps was suggested through estrogen-related and non-estrogen related ways; the two ways can overlap. The most implied factors in the development of endometrial polyps are linked with one of these or both ways.

Behaviour of lab parameters and neonatal weight loss in relation to neonatal breathing movements and cord clamping time.

BACKGROUND: To date, delaying cord clamping two to three minutes after birth is considered effective for newborn well-being. This time does not consider the newborn's breathing movements, which may also condition neonate well-being. AIM: To investigate the behaviour of neonatal weight loss and of some umbilical vein lab parameters, in relation to timing of newborn breathing and cord clamping. MATERIALS AND METHODS: Time from birth to cord clamping and time from birth to first cry of the newborn were collected in 87 full-term healthy women. First cry is a sign of effective breathing. Birth weight loss at the first, second, and third day from birth and lab parameters were assessed in relation to: time from birth to cord clamping, time from birth to first cry, and cord clamping before or after the first cry. RESULTS: Partial pressure of carbon dioxide (pCO2) decreased if cord clamping was performed after first cry and increased if first cry occurred after cord clamping, independently from the time elapsed from birth to first cry (p = 0.012). Calcium (Ca(2+)) concentration decreased if cord clamping was performed after the first cry and increased if first cry of the baby after birth was delayed (p = 0.021). Each second of delay from birth to cord clamping resulted in an increase in Cl- concentration (p <0.001). Each second of delay in cord clamping resulted in a reduction in the percentage of weight loss at the first day (p = 0.024), at the second day (p = 0.007), and at the third day (p = 0.028) after birth. CONCLUSIONS: Neonate breathing after birth should induce umbilical vein flow from placenta to lungs, conditioning the reduction of birth weight loss after birth and umbilical lab parameters modifications.

Could endometrial cytology be helpful in detecting endometrial malignancies?

This short communication assesses the concordance indexes between hysteroscopic biopsies and endometrial cytology for each endometrial pattern found in a sample of 37 women. Patients underwent endometrial cytology under sonographic guidance. The specimens were obtained with an endocervical brush and were fixed on slides (no liquid-based methods). After endometrial cytology, hysteroscopy with biopsy was performed. The best concordance index was found for endometrial malignancies, suggesting that endometrial cytology is able to detect cancers but not other endometrial diseases, as compared with endometrial hysteroscopic biopsies. Therefore, the overall concordance index suggests a fair concordance between histological and cytological findings. This leads us to conclude that usual endometrial cytology should not be recommended to screen endometrial diseases, but it may be used as an alternative diagnostic tool when hysteroscopic biopsies or other blinded procedures for endometrial sampling are unwanted, because it allows malignancies to be detected as well as hysteroscopic-guided biopsies.

Pain and breastfeeding: a prospective observational study.

OBJECTIVE: To demonstrate that pain affects the goodness of breastfeeding. MATERIALS AND METHODS: Seventy-nine patients were interviewed regarding satisfaction in breastfeeding, tiredness, uterine pain, nipple and other pain, and analgesic use at day three and at first, second, third, and fourth week after birth. Data regarding the mode of delivery were recorded from medical charts. Milk formula supplements, bottle use, pacifier use, and nipple shields use were considered as variables suggesting unsuccessful breastfeeding. RESULTS: At third day after delivery, it appeared that analgesic use was significantly associated with milk formula supplementing, bottle use, less satisfaction in breastfeeding, and more tiredness. At first week after delivery, the presence of pain differing from nipple and uterine pain, was more likely associated with milk formula supplementing, bottle use, pacifier use, less satisfaction in breastfeeding, and more tiredness. At third week after delivery, nipple pain was directly related to tiredness, while it increased the odds of adding milk formula and using a bottle. CONCLUSION: Pain affects the goodness of breastfeeding.

Effect of epidural analgesia on labor times and mode of delivery: a prospective study.

PURPOSE: To assess changes in labor times and delivery outcome in low-risk women requesting pain relief and undergoing epidural analgesia, according to the epidural analgesia schemes. MATERIALS AND METHODS: Prospective observational study of 499 low-risk women with epidural analgesia. Speed of dilatation (SD) (centimeters of dilatation / hours), speed of lowering of the fetal head through maternal pelvis (SL) (centimeters in lowering / hours), time of active phase of labor (TA), cesarean section (CS), vacuum application (VA) were dependent variables in multivariable linear and logistic regressions. RESULTS: Dilution of ropivacain, fentanyl amount, and volume of the first dose of epidural analgesia did not seem to affect labor times. Epidural analgesia with schemes used in this study favored both the dilatation and the fetal head lowering through maternal pelvis. Every five minutes from the first dose of epidural to the last top-up, SD decreased by about 13% (p=0.002), SL decreased by about 14% (p<0.001), and TA increased by about 40% (p<0.001). Additionally, every five minutes from the first dose of epidural to the last top-up, the odds of an operative vaginal birth (vacuum) increased by 0.7% (p<0.001). Increasing of number of top-ups independently caused a reduction in odds of undergoing CS (odds ratio 0.434; C.I. 95% 0.219-0.859, p=0.017), without influencing labor times. CONCLUSION: Epidural analgesia in patients requesting pain relief favors normal course of labor if it is not discontinued or delayed.

Modulation of motor cortex neuronal networks by rTMS: comparison of local and remote effects of six different protocols of stimulation.

Repetitive transcranial magnetic stimulation (rTMS) of human motor cortex can produce long-lasting changes in the excitability of excitatory and inhibitory neuronal networks. The effects of rTMS depend critically on stimulus frequency. The aim of our present study was to compare the effects of different rTMS protocols. We compared the aftereffects of 6 different rTMS protocols [paired associative stimulation at interstimulus intervals of 25 (PAS(25)) and 10 ms (PAS(10)); theta burst stimulation delivered as continuous (cTBS) or intermittent delivery pattern (iTBS); 1- and 5-Hz rTMS] on the excitability of stimulated and contralateral motor cortex in 10 healthy subjects. A pronounced increase of cortical excitability, evaluated by measuring the amplitude of motor evoked potentials (MEPs), was produced by iTBS (+56%) and PAS(25) (+45%). Five-hertz rTMS did not produce a significant increase of MEPs. A pronounced decrease of cortical excitability was produced by PAS(10) (-31%), cTBS (-29%), and 1-Hz rTMS (-20%). Short-interval intracortical inhibition was suppressed by PAS(10). Cortical silent period duration was increased by 1-Hz stimulation. No significant effect was observed in the contralateral hemisphere. Head-to-head comparison of the different protocols enabled us to identify the most effective paradigms for modulating the excitatory and inhibitory circuits activated by TMS.

Effect of epidural analgesia on operative vaginal birth rate.

The aim of the study was to investigate if epidural analgesia may affect the operative vaginal birth rate. An observational study was carried out on 1,158 in low-risk patients who delivered vaginally; 46.9% of these patients underwent epidural analgesia using different doses and drugs. Overall, epidural analgesia enhanced the probability of vacuum delivery (OR 2.70 95% CI 1.88-3.89, p < 0.001). Vacuum application was increased about seven times by administration of fentanyl alone at the first dose, while it was reduced if ropivacaine was added to fentanyl. In patients undergoing epidural analgesia, increasing the amount of ropivacaine at the first dose reduced the probability of vacuum delivery (OR 0.82; 95% CI 0.67-1.00, p = 0.05). Moreover, increasing the number of top-ups reduced the probability of vacuum delivery (OR 0.49 95% CI 0.27-0.93, p = 0.029) and the time of the second stage of labor. On the other hand, increasing time from the first dose of epidural to the last top-up increased the risk of operative vaginal delivery (OR 1.33 95% CI 1.03-1.72, p = 0.031) and the time of the second stage of labor. Epidural analgesia seems to favor spontaneous delivery when it is properly carried on.

Enhanced human brain associative plasticity in Costello syndrome.

Costello syndrome (CS) is a rare multiple congenital anomaly disorder which is caused by germline mutations in the v-Ha-ras Harvey rat sarcoma viral oncogene homologue (HRAS) proto-oncogene. Experimental data suggest perturbing effects of the mutated protein on the functional and structural organization of networks of cerebral cortex and on the activity-dependent strengthening of synaptic transmission known as long term potentiation (LTP). In five patients with molecularly proven diagnosis of CS and in a group of 13 age-matched control subjects we investigated activity-dependent synaptic plasticity. To this end, we used a paired associative stimulation (PAS) protocol, in which left ulnar nerve stimuli were followed by transcranial magnetic stimulation (TMS) pulses to right cortical hand area, and recorded motor evoked potentials (MEPs) by single pulse TMS from left first dorsal interosseus (FDI) muscle before and after PAS. In 4 out of 5 CS patients and in a subgroup of nine control subjects we also evaluated the time course and the topographical specificity of PAS after-effects. In these two subgroups, MEPs were measured before, immediately after and 30 min after PAS in the left FDI and left abductor pollicis brevis (APB). While the PAS protocol led to a 65% increase of the FDI MEP amplitude in controls, the LTP-like phenomenon was significantly more pronounced in CS patients, with motor responses increased by 230%. In addition, CS patients showed a similar MEP increase in both muscles while control subjects showed a slight increase in APB and only immediately after PAS. We hypothesize that the extremely enhanced PAS after-effects could be due to the influence of HRAS activity on the susceptibility of synapses to undergo LTP.

Impact of the medicalization of labor on mode of delivery.

AIMS: To evaluate whether routine medical interventions during labor (oxytocin augmentation, induction, amniotomy, epidural analgesia) condition the outcome of delivery independently of each other and of obstetric risk (calculated in an objective manner). Moreover, to evaluate whether there is an ideal window for initiating such interventions. METHODS: Prospective, observational study with 1,047 patients enrolled. RESULTS: Medical interventions were high, whether in low-, medium- or high-risk pregnancies. Oxytocin augmentation (odds ratio 4.678) labour induction (odds ratio 1.717) amniotomy (odds ratio 1.403) and obstetric risk (intermediate-risk odds ratio 1.889, high-risk odds ratio 2.008) increase the probability of an operative delivery. Oxytocin augmentation increases both the probability of a Cesarean delivery and vacuum extraction. Epidural analgesia reduces the probability of cesarean delivery and increases the probability of vacuum extraction. The greater the cervical dilation when oxytocin infusion is initiated, the lower the probability of an operative delivery. The more advanced the cervical dilation and the lower the station when amniotomy or epidural analgesia are carried out, the lower the probability of an operative delivery. Obstetric risk and oxytocin augmentation appear to increase the probability of operative delivery in patients who have undergone amniotomy or epidural analgesia. In addition, labor induction in patients who undergo epidural analgesia increases the risk of operative delivery. CONCLUSIONS: Medical interventions during labor are high and cause a rise in operative delivery. Therefore, practitioners should defer it as much as possible. The exception is epidural analgesia because it seems to reduce the number of cesarean sections.

Cortical plasticity after hand prostheses use: Is the hypothesis of deafferented cortex "invasion" always true?

OBJECTIVE: To study motor cortex plasticity after a period of training with a new prototype of bidirectional hand prosthesis in three left trans-radial amputees, correlating these changes with the modification of Phantom Limb Pain (PLP) in the same period. METHODS: Each subject underwent a brain motor mapping with Transcranial Magnetic Stimulation (TMS) and PLP evaluation with questionnaires during a six-month training with a prototype of bidirectional hand prosthesis. RESULTS: The baseline motor maps showed in all three amputees a smaller area of muscles representation of the amputated side compared to the intact limb. After training, there was a partial reversal of the baseline asymmetry. The two subjects affected by PLP experienced a statistically significant reduction of pain. CONCLUSIONS: Two apparently opposite findings, the invasion of the "deafferented" cortex by neighbouring areas and the "persistence" of neural structures after amputation, could vary according to different target used for measurement. Our results do not support a correlation between PLP and motor cortical changes. SIGNIFICANCE: The selection of the target and of the task is essential for studies investigating motor brain plasticity. This study boosts against a direct and unique role of motor cortical changes on PLP genesis.

Early diagnosis of Alzheimer's disease: the role of biomarkers including advanced EEG signal analysis. Report from the IFCN-sponsored panel of experts.

Alzheimer's disease (AD) is the most common neurodegenerative disease among the elderly with a progressive decline in cognitive function significantly affecting quality of life. Both the prevalence and emotional and financial burdens of AD on patients, their families, and society are predicted to grow significantly in the near future, due to a prolongation of the lifespan. Several lines of evidence suggest that modifications of risk-enhancing life styles and initiation of pharmacological and non-pharmacological treatments in the early stage of disease, although not able to modify its course, helps to maintain personal autonomy in daily activities and significantly reduces the total costs of disease management. Moreover, many clinical trials with potentially disease-modifying drugs are devoted to prodromal stages of AD. Thus, the identification of markers of conversion from prodromal form to clinically AD may be crucial for developing strategies of early interventions. The current available markers, including volumetric magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebral spinal fluid (CSF) analysis are expensive, poorly available in community health facilities, and relatively invasive. Taking into account its low cost, widespread availability and non-invasiveness, electroencephalography (EEG) would represent a candidate for tracking the prodromal phases of cognitive decline in routine clinical settings eventually in combination with other markers. In this scenario, the present paper provides an overview of epidemiology, genetic risk factors, neuropsychological, fluid and neuroimaging biomarkers in AD and describes the potential role of EEG in AD investigation, trying in particular to point out whether advanced analysis of EEG rhythms exploring brain function has sufficient specificity/sensitivity/accuracy for the early diagnosis of AD.

LTD-like plasticity induced by paired associative stimulation: direct evidence in humans.

Paired associative stimulation (PAS), in which peripheral nerve stimuli are followed by transcranial magnetic stimulation (TMS) of the motor cortex, may produce a long lasting change in cortical excitability. At an interstimulus interval slightly shorter than the time needed for the afferent inputs to reach cerebral cortex (10 ms), motor cortex excitability decreases. Indirect data support the hypothesis that PAS at this interval (PAS10) involves LTD like-changes in cortical synapses. The aim of present paper was to investigate more directly PAS10 effects. We recorded corticospinal descending volleys evoked by single pulse TMS before and after PAS10 in two conscious subjects who had a high cervical epidural electrode implanted for pain control. These synchronous volleys provide a measure of cortical synaptic activity. PAS10 significantly reduced the amplitude of later descending waves while the earliest descending wave was not modified. Present results confirm the cortical origin of the effect of PAS10.

Characterization of multi-channel intraneural stimulation in transradial amputees.

Although peripheral nerve stimulation using intraneural electrodes has been shown to be an effective and reliable solution to restore sensory feedback after hand loss, there have been no reports on the characterization of multi-channel stimulation. A deeper understanding of how the simultaneous stimulation of multiple electrode channels affects the evoked sensations should help in improving the definition of encoding strategies for bidirectional prostheses. We characterized the sensations evoked by simultaneous stimulation of median and ulnar nerves (multi-channel configuration) in four transradial amputees who had been implanted with four TIMEs (Transverse Intrafascicular Multichannel Electrodes). The results were compared with the characterization of single-channel stimulation. The sensations were characterized in terms of location, extent, type, and intensity. Combining two or more single-channel configurations caused a linear combination of the sensation locations and types perceived with such single-channel stimulations. Interestingly, this was also true when two active sites from the same nerve were stimulated. When stimulating in multi-channel configuration, the charge needed from each electrode channel to evoke a sensation was significantly lower than the one needed in single-channel configuration (sensory facilitation). This result was also supported by electroencephalography (EEG) recordings during nerve stimulation. Somatosensory potentials evoked by multi-channel stimulation confirmed that sensations in the amputated hand were perceived by the subjects and that a perceptual sensory facilitation occurred. Our results should help the future development of more efficient bidirectional prostheses by providing guidelines for the development of more complex stimulation approaches to effectively restore multiple sensations at the same time.

Methods for analysis of brain connectivity: An IFCN-sponsored review.

The goal of this paper is to examine existing methods to study the "Human Brain Connectome" with a specific focus on the neurophysiological ones. In recent years, a new approach has been developed to evaluate the anatomical and functional organization of the human brain: the aim of this promising multimodality effort is to identify and classify neuronal networks with a number of neurobiologically meaningful and easily computable measures to create its connectome. By defining anatomical and functional connections of brain regions on the same map through an integrated approach, comprising both modern neurophysiological and neuroimaging (i.e. flow/metabolic) brain-mapping techniques, network analysis becomes a powerful tool for exploring structural-functional connectivity mechanisms and for revealing etiological relationships that link connectivity abnormalities to neuropsychiatric disorders. Following a recent IFCN-endorsed meeting, a panel of international experts was selected to produce this current state-of-art document, which covers the available knowledge on anatomical and functional connectivity, including the most commonly used structural and functional MRI, EEG, MEG and non-invasive brain stimulation techniques and measures of local and global brain connectivity.

Intravaginal gemeprost and second-trimester pregnancy termination in the scarred uterus.

OBJECTIVE: To investigate the effectiveness and complication rate of intravaginal gemeprost, a prostaglandin E(1) analogue, for second-trimester pregnancy termination in women with a scarred uterus. METHODS: Of 439 women undergoing induced abortion between the 13th and the 23rd week of pregnancy, 67 had a scarred uterus because of 1 or more cesarean sections or myomectomy. All women received a 1 mg dose of gemeprost intravaginally every 3 h, up to 5 times over 24 h. Those who did not respond received further cycles of gemeprost treatment. RESULTS: The rate of successful abortions among women with uterine scars was not different from that observed in the nulliparous controls, but previously vaginal delivery was associated with a shorter induction to abortion interval. The rate of severe complications did not differ between the groups, and was about 1%. CONCLUSION: The rate of complications following intravaginal administration of a PGE(1) analogue for second-trimester pregnancy termination was similar in women with a scarred or unscarred uterus.

Alpha Lipoic Acid (ALA) effects on subchorionic hematoma: preliminary clinical results.

OBJECTIVE: The clinic use of alpha Lipoic Acid (ALA) is linked to its capability to exert antioxidant effects and, more interestingly, to counteract the pathologic changes of complex networks of cytokines, chemokines and growth factors, restoring their physiological state. The aim of this randomized controlled clinical trial was to test the contribution of oral supplementation of ALA to the standard treatment with Progesterone vaginal suppositories, in healing subchorionic hematomas in patients with threatened miscarriage. Controls were administered only Progesterone suppositories. PATIENTS AND METHODS: Nineteen pregnant women in the first trimester of gestation, with threatened miscarriage and ultrasound evidence of subchorionic hematoma, were included in the trial and randomly divided in two groups: controls, treated with 400 mg Progesterone (200 mg 2 times per day), given by vaginal suppositories, and case study treated with the same Progesterone dosage, plus ALA, given orally at the dose of 600 mg (300 mg 2 times per day, DAV®, Lo.Li. Pharma srl, Italy). Sixteen patients completed the trial. Treatment was performed until complete resolution of the clinical picture. RESULTS: In both groups, the subjects improved significantly but, in general, a better and faster evolution in the major signs of threatened miscarriage was observed in the subjects treated with ALA and Progesterone. In these patients, the speed of resorption of subchorionic hematoma was significantly (p ≤ 0.05) superior compared to controls. The ALA and Progesterone group showed a faster decrease or disappearance of all symptoms than that observed in the control group, however the difference was not significant. CONCLUSIONS: These preliminary results suggest that ALA supplementation significantly contributes to speed up the process of restoration of physiological conditions in threatened miscarriage and ameliorates the medical conditions of both the mothers and the foetus, probably modulating the networks of cytokines, growth factors and other molecules.

External cephalic version for singleton breech presentation: proposal of a practical check-list for obstetricians.

OBJECTIVE: External cephalic version (ECV) for breech presentation is not routinely performed by obstetricians in many clinical settings. The aim of this work is to assess to what extent the factors involved in performing ECV are relevant for the success and safety of ECV, in order to propose a practical check-list for assessing the feasibility of ECV. METHODS: Review of 214 references. Factors involved in the success and risks of ECV (feasibility of ECV) were extracted and were scored in a semi-quantitative way according to textual information, type of publication, year of publication, number of cases. Simple conjoint analysis was used to describe the relevance found for each factor. RESULTS: Parity has the pivotal role in ECV feasibility (relevance 16.6%), followed by tocolysis (10.8%), gestational age (10.6%), amniotic fluid volume (4.7%), breech variety (1.9%), and placenta location (1.7%). Other factors with estimated relevance around 0 (regional anesthesia, station, estimated fetal weight, fetal position, obesity/BMI, fetal birth weight, duration of manoeuvre/number of attempts) have some role in the feasibility of ECV. Yet other factors, with negative values of estimated relevance, have even less importance. CONCLUSIONS: From a logical interpretation of the relevance of each factor assessed, ECV should be proposed with utmost prudence if a stringent check-list is followed. Such a check-list should take into account: parity, tocolytic therapy, gestational age, amniotic fluid volume, breech variety, placenta location, regional anesthesia, breech engagement, fetal well-being, uterine relaxation, fetal size, fetal position, fetal head grasping capability and fetal turning capability.

Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee.

These guidelines provide an up-date of previous IFCN report on "Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application" (Rossini et al., 1994). A new Committee, composed of international experts, some of whom were in the panel of the 1994 "Report", was selected to produce a current state-of-the-art review of non-invasive stimulation both for clinical application and research in neuroscience. Since 1994, the international scientific community has seen a rapid increase in non-invasive brain stimulation in studying cognition, brain-behavior relationship and pathophysiology of various neurologic and psychiatric disorders. New paradigms of stimulation and new techniques have been developed. Furthermore, a large number of studies and clinical trials have demonstrated potential therapeutic applications of non-invasive brain stimulation, especially for TMS. Recent guidelines can be found in the literature covering specific aspects of non-invasive brain stimulation, such as safety (Rossi et al., 2009), methodology (Groppa et al., 2012) and therapeutic applications (Lefaucheur et al., 2014). This up-dated review covers theoretical, physiological and practical aspects of non-invasive stimulation of brain, spinal cord, nerve roots and peripheral nerves in the light of more updated knowledge, and include some recent extensions and developments.

Adrenomedullin, a new vasoactive peptide, is increased in preeclampsia.

Adrenomedullin is a novel peptide that elicits a long-lasting vasorelaxant activity. Recently, we found high concentrations of adrenomedullin in maternal and umbilical cord plasma and in amniotic fluid in full-term human pregnancy, indicating a role of this peptide during gestation. To investigate the possibility that adrenomedullin is involved in the pathophysiology of preeclampsia, we measured its concentration in maternal and fetoplacental compartments. We studied 12 normotensive nonpregnant women, 13 hypertensive nonpregnant subjects, 29 patients with preeclampsia, and 30 normotensive pregnant women. In all patients, plasma was collected from the cubital vein, and amniotic fluid samples were obtained by transabdominal amniocentesis or at elective cesarean section. Plasma samples from umbilical vein and placental tissues were collected at delivery. Adrenomedullin was assayed on plasma and amniotic fluid samples using a specific radioimmunoassay, and its localization and distribution on placental sections was determined by immunohistochemistry. Adrenomedullin concentrations were higher in hypertensive than in normotensive nonpregnant patients. Pregnant women had higher adrenomedullin levels than nonpregnant subjects, although maternal plasma adrenomedullin concentrations did not differ between normal pregnant and preeclamptic women. Preeclamptic patients showed higher concentrations (P<0.01) than normotensive pregnant women of adrenomedullin in amniotic fluid (252+/-29 versus 112+/-10 fmol/ micromol creatinine) and umbilical vein plasma (18.1+/-2.1 versus 8. 5+/-1.1 fmol/mL). Increased local production of adrenomedullin is associated with preeclampsia. The fetus seems to be responsible for the higher levels of this hormone. Increased adrenomedullin concentrations may be necessary to maintain placental vascular resistance and/or fetal circulation at a physiological level.