Severe Bartter syndrome type 1: Prompt postnatal management thanks to antenatal identification of SLC12A1 pathogenic variants.

Bartter syndrome (BS) refers to a group of hereditary kidney disorders. One antenatal form is Bartter syndrome type 1 (BS1), caused by pathogenic variants in the SLC12A1 gene. We report a case of BS1 presenting with severe polyhydramnios. The fetus was found to carry three pathogenic variants of SLC12A1, leading to the antenatal diagnosis of BS1 and its prompt management. At age 18 days, clinical conditions were complicated by the onset of sepsis requiring supportive measures as well as steroid and antibiotic therapy. Any newborn with an antenatal history of polyhydramnios or postnatal polyuria should be suspected of having BS, since delayed diagnosis may lead to rapid renal failure.

Ovotoxicity of smoking and impact on AMH levels: a pilot study.

OBJECTIVE: Our study aims to analyze the correlation between the decrease of ovarian reserve and lower oocyte quality produced by the follicle associated with use of tobacco. In particular, the study analyzed the potential effects of cigarette smoking on hormonal dosages in infertile patients and patients with recurrent miscarriages. PATIENTS AND METHODS: This retrospective study included 61 women with a history of infertility and recurrent miscarriage between March 2016 and March 2019 selected at the clinic of poly-abortivity and infertility at the ASL Roma 2 - Department of Obstetrics and Gynecology, "S. Eugenio" Hospital. Patients' medical history (familiar, physiological and pathological with particular attention to smoking habits and nutrition), the obstetric history, gynecological examination and ultrasound were recorded. The serum concentration of FSH, AMH, Inhibin B were examined between the second and third day of the period. RESULTS: A total of 61 patients between 25 and 43 years of age admitted into our clinic were identified; 42 patients with a history of recurrent abortion (more than two abortions) and 19 patients with a history of infertility were selected. A total of 31 non-smokers women (50.82%) (G1) and 30 (49.18%) (G2) smokers were included. No differences were detected between the two groups under examination; the parameter that did appear discordant is the AMH value; this value scored higher in non-smokers than in smokers. Specifically, in smoker patients with recurrent abortions. CONCLUSIONS: The connection between nicotine, combustion material, and oocyte quality is an important and controversial research topic. Further studies are needed to clarify the influence of nicotine and combustion on the ovarian reserve in order to identify the main risk factors.

Emergency Contraception: are the rights to conscience and to reproductive freedom irreconcilable?

Emergency Contraception (EC) has been gaining attention for its controversial nature, from the ethical, moral and religious perspectives. Objecting health professionals feel that the implementation of certain procedures or the prescription of some drugs would engender a conflict of conscience. That is also true in the context of reproductive medicine and not only limited to EC, but including abortion and some medically-assisted procreation procedures; all such procedures have created a rift between sexuality and procreation that has substantial ethical complexities. Provided that respect for conscience is essential, and codified in many national and international statutes, any refusal to provide services or medication should be limited if it might negatively affect a patient's health, is based on scientific misinformation, or could bring about inequalities of any kind. First and foremost, any imposition of religious or moral beliefs on patients should not be countenanced. In fact, any form of conscientious objection that could harm patient well-being should be allowed only if the fundamental duty towards patients can be effectively discharged. The right to thorough and unbiased information is crucial so as to enable patients to make well-informed decisions. Moreover, as the WHO has remarked, access to safe and legal reproductive services should be fostered particularly in at-risk, resource-poor areas.

The potential role of magnetic resonance brain relaxometry in veterinary medicine: a preliminary study.

Magnetic Resonance (MR) is a non-invasive modality of choice for the evaluation of brain morphology, with superior performance as compared to other techniques. However, MR images are typically assessed qualitatively, thus relying on the experience of the involved radiologist. This may lead to errors of interpretation in the presence of subtle alterations and does not exploit the full potential of this technique as a quantitative diagnostic tool. To this end Magnetic Resonance Relaxometry (MRR), which is able to quantitively characterize the tissues under investigation through their relaxation rates, seems extremely promising. Many studies assessed the feasibility of relaxometry as a diagnostic tool in human brain disorders, with the most promising results obtained in the evaluation of neurodegenerative diseases and in the oncologic field. However, despite such extensive literature in human medicine, due to the lack of standardized protocols and the need of high-field MRI scanners, to date few studies have been performed on companion animals. In this work, first we describe relaxometry applications in human neuropathology and their possible extension to companion animals both in the experimental and clinical fields. Then, we present two experiments performed on a typical standard clinical scanner operating at 0.25 T to show that, despite the low field intensity, this technique may be promising even in the clinical setup. We tested the relaxometry protocol in a phantom study and then applied it to a real clinical case study. The results showed that this protocol used on a phantom led to a higher contrast, as compared to the standard approach. Furthermore, when applied to a real case study, this protocol revealed brain lesions undetected by the standard technique which were confirmed by a histopathological examination. These preliminary results are encouraging and support the development of this approach as an advanced diagnostic tool even in a clinical setting where low field MRI scanners are typically employed.

Androgen insensitivity syndrome.

OBJECTIVE: We provide a review of the literature about the Androgen Insensitivity Syndrome (AIS), its onset and associated developmental anomalies and the genetic alterations causing it. MATERIALS AND METHODS: We searched PubMed with a larger emphasis on the physiology, genetics and current management of AIS. RESULTS: AIS is an X-linked recessive Disorder of Sex Development (DSD). It is caused by mutations of the Androgen Receptor, and their large amount and heterogeneity (missense and nonsense mutations, splicing variants, deletions, and insertions) are responsible for the wide spectrum of possible phenotypes of patients, divided into Partial AIS (PAIS) and Complete AIS (CAIS). Once the clinical and laboratory investigations have laid the foundation for a diagnostic hypothesis, it is important to identify the actual karyotype of the individual and search for the mutation in the Androgen Receptor to diagnose with certainty the syndrome. Alternatively, in the absence of such evidence, the diagnosis should more properly be an AIS-like condition, which we describe as well in our report. CONCLUSIONS: The management of this DSD is based on pharmacotherapies, surgery and psychological support: all of them must be directed to facilitate the patient's life, considering his/her sexual identity.

Medical advancements: emergency contraception (EC). Medico-legal implications of EC on adolescents.

The article's main focus is documenting what the best options are in order to make sure that minors are allowed to play a key role in the management of issues arising from the use of emergency contraception. In that regard, there is a lack of clean-cut legislative measures and, although there are several legal and ethical norms designed to get parents or legal guardians involved in such decisions, there seems to be an increasingly widespread tendency to give weight to the minor's will, thus acknowledging her decision-making capacity. Lastly, the paper's authors undertake a thorough examination as to what the duties of doctors are, and the measures that need to be put in place in order to safeguard the minor patients' conditions. They arrive at the conclusion that emergency contraception is suitable for minors even in absence of the stated consent from their parents or guardians, but it is of utmost importance to implement adequate measures aimed at the provision of proper care, prevention and education.

Vesicoureteral reflux in infants: what do we know about the gender prevalence by age?

OBJECTIVE: Vesicoureteral reflux (VUR) affects up to 1% of Caucasian children. Primary VUR is characterized by failure of the ureterovesicular junction to prevent urine from traveling in a retrograde fashion from the bladder to the ureters and the kidneys. Several reports in the literature describe the prevalence of this condition in pediatric patients; overall, VUR affects more males during infancy and with higher grades. However, a thorough consideration of these articles reveals important contradictions regarding the prevalence by gender and age. We analyzed those contradictions and suggested a possible explanation based on our single center experience with this patient group. In particular, for the age interval 0-2 years: we have found that (1) VUR mostly affects boys; (2) the male/female ratio steadily declines over time; (3) the unequal prevalence between males and females essentially disappears when children reach the age of two years. CONCLUSIONS: The natural history of VUR in infant boys differs from that of infant girls, and therefore requires a gender-specific approach. Available data support the need to redefine the categorization and clinical guidelines for this disease.

2014-2017. How medically assisted reproduction changed in Italy. A short comparative synthesis with European countries.

More than ten years after law n. 40 of February 19, 2004 became effective, regulation on medically assisted reproduction has dramatically changed outlook. The authors report on the steps that led to these changes through Courts' rulings, the Supreme Court's verdicts and the European Court of Human Rights' decisions, as well as ministerial regulations and guidelines concerning medically assisted reproduction. The aforementioned jurisprudential evolution was set to reach a new balance between the embryo's right to its own dignity and the woman's right to health and freedom of self-determination in reproduction. No court ruling denies that embryos have also to be safeguarded. In fact, there are still numerous prohibitions, including using embryos for experimental purposes. Judges aim primarily at avoiding that embryos' rights overcome the right to parenthood. The authors review the legislation of the various European countries: some have adopted a legislation to regulate medically assisted reproduction, while others have developed in this field some recommendations or guidelines. This is why they call for enactment of a European law governing the implementation/operational methods of medically assisted reproduction in order to avoid the scourge of procreative tourism to countries that have a more permissive law.

Relaxant effect of proton pump inhibitors on in vitro myometrium from pregnant women.

AIM: In this study we investigate in in vitro myometrial tissue samples of pregnant women: (a) the effects of proton pomp inhibitors (PPIs) (omeprazole, esomeprazole, pantoprazole, lansoprazole and rabeprazole) on spontaneous contractions; (b) the muscle-relaxant efficacy of the most active PPI considered (pantoprazole) in comparison with that of other known tocolytics (nifedipine, atosiban, MgSO4, isoxsuprine); (c) the effect of pantoprazole on contractions induced by calcium (Ca(++)), KCl, oxytocin and prostaglandin (PGE2); (d) the possible mediators of pantoprazole relaxant effect. METHODS: Organ bath studies were performed on myometrial tissue samples (40×10×10 mm) from pregnant women (38-42 weeks of gestational age) undergoing elective caesarian section. RESULTS: All the PPIs studied reduce the spontaneous contraction of the myometrial smooth muscle. Pantoprazole is the most effective and most potent inhibitor among those analyzed. Pantoprazole also reduces the contractions induced by Ca(++), KCl, oxytocin and PGE2. Neither NO, nor PGs, or the activation of Ca(++)-dependent K(+) currents mediate the muscle-relaxant effect of this PPI. CONCLUSION: These data, together with the fact that PPIs almost do not present side effects, suggest that these drugs can offer new therapeutic strategies for preterm delivery. Undoubtedly, further investigations and clinical studies are necessary before adding PPIs to the list of drugs available for the treatment of preterm delivery.

[Role of beta-glucan in the treatment of recurrent candidiasis and HPV-correlated lesions and reparative process of epidermis]. / Beta-glucano e terapia delle candidosi recidivanti e delle disepitelizzazioni cutanee iatrogene.

AIM: The aim of the study was to examine the effects of beta-glucan treatment in women with recurrent vulvar candidiasis or previously treated with diathermocoagulation (DTC) for vulvar lesions caused by human papillomavirus (HPV) infection. METHODS: From January to March 2008, 23 women with a history of recurrent candidiasis and 209 women who underwent to DTC for HPV-correlated vulvar lesions were recruited at the Department of Obstetrics and Gynaeco-logy of San Camillo-Forlanini Hospital of Rome. The two groups were treated with two cycles of a daily topical application of beta-glucan for 15 consecutive days with a suspension of 20 days. The effects of beta-glucan were analyzed at the 1st and the 3rd month from the start of the therapy. RESULTS: A total of 209 women, 21 with recurrent candidiasis and 188 who underwent to DTC for HPV-correlated lesions, completed the study. After the first month of treatment we not found any evidence of disease in both groups; otherwise we observed, a month after the term of the therapy, 5% and 3% of recurrence of candidiasis or lesions secondary to HPV infection, respectively, even if with low grade. CONCLUSIONS: Our results demonstrate the efficacy of beta-glucan treatment for recurrent candidiasis, HPV-correlated lesions and in the reparative process of epidermis.

Umbilical cord interleukin-6 levels are elevated in term neonates with perinatal asphyxia.

BACKGROUND: A correlation between elevation of pro-inflammatory cytokines and white matter injury or abnormal neurologic outcome has been established in the preterm infant. In the full-term neonate, few studies exist linking elevation of cytokines with encephalopathy and poor neurodevelopmental outcome. Our aims were to investigate if serum interleukin-6 concentrations in delivering mothers and their offspring at birth are associated with perinatal asphyxia, and to examine the relation of interleukin-6 levels to the severity of hypoxic-ischemic encephalopathy and to the neurological outcome. DESIGN AND METHODS: Serum interleukin-6 levels were measured at birth, 24 and 48 h of life in 50 consecutive term uninfected newborns with perinatal asphyxia and 113 randomly selected healthy term newborns, and at delivery in their mothers. RESULTS: The median cord interleukin-6 concentrations in the infants who developed hypoxic-ischemic encephalopathy was 376-fold as high as the values in the normal infants (P < 0.0001) and 5.5-fold as high as those in the infants with asphyxia who did not develop hypoxic-ischemic encephalopathy (P < 0.05). There was also a significant relationship between interleukin-6 and the degree of hypoxic-ischemic encephalopathy, and between interleukin-6 and neurodevelopmental outcome at 2 years of age. Regardless of outcome, in the asphyxiated infants the interleukin-6 values were significantly lower at both 24 and 48 h of life than at birth, with a significant decline from 24 to 48 h of life. Among mothers of the asphyxiated neonates, there were no significant differences in interleukin-6 concentrations between those delivering neonates with and without hypoxic-ischemic encephalopathy. CONCLUSIONS: Measurement of IL-6 concentrations in the umbilical cord of neonates with perinatal asphyxia may be useful to identify early, and in a relatively simple way, those who are most likely to have subsequent brain injury and adverse outcome.

Serial measurements of C-reactive protein and interleukin-6 in the immediate postnatal period: reference intervals and analysis of maternal and perinatal confounders.

BACKGROUND: There is a wide range of reported sensitivities and specificities for C-reactive protein (CRP) and interleukin-6 (IL-6) in the detection of early-onset neonatal infection. This prompted us to assess reference intervals for CRP and IL-6 during the 48-h period immediately after birth and to identify maternal and perinatal factors that may affect them. METHODS: CRP and IL-6 values were prospectively obtained for 148 healthy babies (113 term, 35 near-term) at birth and at 24 and 48 h of life, and from their mothers at delivery. RESULTS: Upper reference limits for CRP at each neonatal age were established. At birth, CRP was significantly lower than at 24 and 48 h of life. Rupture of membranes > or =18 h, perinatal distress, and gestational hypertension significantly affected the neonatal CRP dynamics, but at specific ages. There was no correlation between CRP concentrations in mothers and their offspring at birth. The IL-6 values observed in the delivering mothers and in their babies at all three neonatal ages were negatively associated with gestational age. In the immediate postnatal period, IL-6 dynamics for term babies were significantly different from those for near-term babies. Maternal IL-6 concentrations correlated with babies' IL-6 concentrations only for term deliveries. Apgar score had a significant effect on babies' IL-6 values at birth. CONCLUSIONS: The patterns of CRP and IL-6 responses in the healthy neonate should be taken into account to optimize their use in the diagnosis of early-onset neonatal sepsis.

Serum procalcitonin concentrations in term delivering mothers and their healthy offspring: a longitudinal study.

BACKGROUND: The reported sensitivities and specificities of procalcitonin (PCT) concentrations for the diagnosis of neonatal infection vary widely. A postnatal increase of PCT has been observed in healthy term newborns with a peak at approximately 24 h of age, and many questions remain regarding maternal and perinatal factors that may influence the normal PCT kinetics during the immediate postnatal period. METHODS: We prospectively investigated the association between the serum PCT values obtained from 121 mothers at delivery and serum PCT in their healthy, term offspring at birth as well as at 24 and 48 h of age. We also analyzed whether obstetric and perinatal factors would alter maternal and neonatal PCT response. RESULTS: PCT concentrations in the babies at birth were significantly higher than in the mothers (P <0.0001), with even larger differences at 24 and 48 h of age. None of the variables identified from maternal and perinatal histories had a significant effect on maternal PCT response. In the healthy neonate, the variables that significantly affected the concentration of PCT at birth were the mothers' PCT (P <0.01), maternal group B streptococcus colonization (P <0.05), and rupture of membranes >/=18 h (P <0.01). The coefficient of linear correlation between the mother's PCT concentration and that of the baby at birth was 0. 32 (P <0.01). The only variable that significantly altered the PCT concentration at both 24 (P <0.01) and 48 (P <0.01) h of age was rupture of membranes >/=18 h. Nonetheless, the PCT response observed during the 48-h period after birth among healthy babies born to mothers with risk factors for infection was well below that reported previously among age-matched neonates with sepsis. CONCLUSIONS: The postnatal increase of PCT observed in the healthy neonate with peak values at 24 h of age most likely represents endogenous synthesis. In estimating the sensitivities and specificities of PCT for diagnosis of sepsis throughout the initial 48 h of life, it is important to consider the normal PCT kinetics and the pattern(s) of PCT response in the healthy neonate.

Dissociation kinetics of hemocyanin from Octopus vulgaris.

The native form of hemocyanin (Hc) from Octopus vulgaris can be completely dissociated, at alkaline pH and in the presence of EDTA, from 49S decamers to 11S monomers. The kinetics of this process was studied, using a Bio-Logic stopped flow system, by following the time dependence of the 450-nm light intensity, scattered at 90 degrees, in the 7.9-8.8 pH range. All experimental traces were best fitted by a sum of three exponential decay functions. We then tried to best fit these decay functions with a series of kinetic models, the best of them resulting in one whose dissociation of decamers to monomers takes place in three consecutive and irreversible steps, with a highly cooperative step concerning dissociation of octamers to dimers, which appears to be the only intermediate species. This model was preferred over several others, not only for the best norm value but also for the best accordance between each calculated and experimental kinetic parameter (rate constants and amplitudes). Although other more complex models may be considered, our best fit model represents the simplest one, which is able to describe the observed dissociation kinetics.