The impact of resveratrol on the outcome of the in vitro fertilization: an exploratory randomized placebo-controlled trial.

BACKGROUND: Resveratrol is a natural polyphenolic compound present in plants and red wine with many potential health benefits. This compound has various anti-inflammatory and anti-tumor properties and can improve cellular mitochondrial activity. This trial was designed to evaluate the effect on the outcome of IVF of Resveratrol supplementation in women > 35 years with good ovarian reserve (AMH > 1.2 ng/ml). Women were randomized to receive or placebo or Resveratrol (150 mg per day) for three months preceding the ovarian stimulation (OS). All patients were stimulated with a starting dose of recombinant FSH ranging between 150 and 300 IU according to age and ovarian reserve. GnRH antagonist flexible protocol was adopted for pituitary suppression. Triggering was performed with urinary hCG (10.000 IU). RESULTS: The study was conducted between January 2019 and December 2022 with aa total of 37 cases and 33 controls were recruited. No statistically significant differences in the number of oocytes retrieved, biochemical pregnancy, clinical pregnancy and live birth rates were observed between women treated with resveratrol and control group. A statistically significant increase in the follicle output rate (FORT) and follicle-to oocyte index (FOI) was observed in women treated with resveratrol-based nutraceutical (0.92 versus 0.77 [p = 0.02], and 0.77 versus 0.64 [p = 0.006], respectively). CONCLUSIONS: Preliminary results from this study indicate that pre-treatment with resveratrol may improve ovarian sensitivity to exogenous FSH, which in turn may decrease the risk of hypo-response to OS in advanced reproductive age women.

The impact of modern radiotherapy on long-term cardiac sequelae in breast cancer survivor: a focus on deep inspiration breath-hold (DIBH) technique.

INTRODUCTION: One of the most feared side effects of radiotherapy (RT) in the setting of breast cancer (BC) patients is cardiac toxicity. This side effect can jeopardize the quality of life (QoL) of long-term survivors. The impact of modern techniques of RT such as deep inspiration breath hold (DIBH) have dramatically changed this setting. We report and discuss the results of the literature overview of this paper. MATERIALS AND METHODS: Literature references were obtained with a PubMed query, hand searching, and clinicaltrials.gov. RESULTS: We reported and discussed the toxicity of RT and the improvements due to the modern techniques in the setting of BC patients. CONCLUSIONS: BC patients often have a long life expectancy, thus the RT should aim at limiting toxicities and at the same time maintaining the same high cure rates. Further studies are needed to evaluate the risk-benefit ratio to identify patients at higher risk and to tailor the treatment choices.

Autosomal-dominant myopia associated to a novel P4HA2 missense variant and defective collagen hydroxylation.

We recently described a complex multisystem syndrome in which mild-moderate myopia segregated as an independent trait. A plethora of genes has been related to sporadic and familial myopia. More recently, in Chinese patients severe myopia (MYP25, OMIM:617238) has been linked to mutations in P4HA2 gene. Seven family members complaining of reduced distance vision especially at dusk underwent complete ophthalmological examination. Whole-exome sequencing was performed to identify the gene responsible for myopia in the pedigree. Moderate myopia was diagnosed in the family which was associated to the novel missense variant c.1147A > G p.(Lys383Glu) in the prolyl 4-hydroxylase,alpha-polypeptide 2 (P4HA2) gene, which catalyzes the formation of 4-hydroxyproline residues in the collagen strands. In vitro studies demonstrated P4HA2 mRNA and protein reduced expression level as well as decreased collagen hydroxylation and deposition in mutated fibroblast primary cultures compared to healthy cell lines. This study suggests that P4HA2 mutations may lead to myopic axial elongation of eyeball as a consequence of quantitative and structural alterations of collagen. This is the first confirmatory study which associates a novel dominant missense variant in P4HA2 with myopia in Caucasian patients. Further studies in larger cohorts are advisable to fully clarify genotype-phenotype correlations.

Perceived insecurity, mental health and urbanization: Results from a multicentric study.

AIMS: This article aims to (1) explore the levels of perceived insecurity in a sample of patients with mood or anxiety disorders and (2) assess whether living in 'big cities' can influence the levels of patients' perceived insecurity and social contacts compared to living in a non-urbanized context. METHODS: A total of 24 Italian mental health centers (MHCs) have been invited to participate. Twenty patients consecutively accessing the MHC have been recruited. All patients have been assessed using validated assessment tools. RESULTS: The sample consisted of 426 patients, mostly female, with a mean age of 45 years. Globally, 52.2% of patients had a diagnosis of mood disorders, and 37.8% had anxiety disorders. Half of the sample declared that the main feeling toward life is uncertainty; higher levels of pessimistic views toward life have been detected in patients living in urban areas. A positive association between negative attitudes toward life and higher levels of depressive and anxiety symptoms, poor social functioning and higher levels of perceived psychological distress has been found. CONCLUSION: Our findings confirm the presence of a common sense of perceived uncertainty among our sample. Such attitude toward life can have a detrimental impact on patients' psychological and physical well-being, contributing to high levels of distress.

Lymphocytosis as a response biomarker of natalizumab therapeutic efficacy in multiple sclerosis.

BACKGROUND: Natalizumab is an effective therapy in relapsing-remitting multiple sclerosis (RRMS), as it reduces lymphocyte transmigration through the blood-brain barrier (BBB) and induces lymphocytosis. OBJECTIVES: To analyse natalizumab-induced lymphocytosis (NIL) as a biomarker of drug efficacy. MATERIALS AND METHODS: We enrolled 50 relapsing-remitting (RR) and progressive-relapsing (PR) natalizumab-treated patients who had received at least 16 infusions and had been tested for lymphocyte count 24 hours before each administration. Clinical, MRI and hematological data were collected. Patients were divided into responders and sub-optimal responders according to the experience of at least one clinical and/or instrumental relapse during the treatment. RESULTS: In 15 (30%) patients, an instrumental/clinical (14) or only instrumental (one) relapse occurred. We found a statistically significant difference in the mean percentage of the lymphocytes between the two groups over the first ten administrations (p=0.04). The comparison between the time-to-relapse in the groups with high and low levels of lymphocytes showed that the group with a low NIL had a greater risk of relapse (p=0.03). CONCLUSIONS: We suggest that NIL could be a biomarker of therapeutic efficacy in patients with RRMS treated with natalizumab, and that the risk of relapse may be higher in patients with a lower-than-expected NIL.

LOPED study: looking for an early diagnosis in a late-onset Pompe disease high-risk population.

OBJECTIVE: A multicentre observational study was aimed to assess the prevalence of late-onset Pompe disease (LOPD) in a large high-risk population, using the dried blood spot (DBS) as a main screening tool. DESIGN/METHODS: 17 Italian neuromuscular centres were involved in the late-onset Pompe early diagnosis (LOPED) study. Inclusion criteria were: (1) age ≥5 years, (2) persistent hyperCKaemia and (3) muscle weakness at upper and/or lower limbs (limb-girdle muscle weakness, LGMW). Acid α-glucosidase (GAA) activity was measured separately on DBS by fluorometric as well as tandem mass spectrometry methods. A DBS retest was performed in patients resulted positive at first assay. For the final diagnosis, GAA deficiency was confirmed by a biochemical assay in skeletal muscle, whereas genotype was assessed by GAA molecular analysis. RESULTS: In a 14-month period, we studied 1051 cases: 30 positive samples (2.9%) were detected by first DBS screening, whereas, after retesting, 21 samples were still positive. Biochemical and molecular genetic studies finally confirmed LOPD diagnosis in 17 cases (1.6%). The median time from the onset of symptoms/signs to diagnosis was 5 years. Among those patients, 35% showed presymptomatic hyperCKaemia and 59% showed hyperCKaemia+LGMW, whereas 6% manifested with LGMW. CONCLUSIONS: LOPED study suggests that GAA activity should be accurately screened by DBS in all patients referring for isolated hyperCKaemia and/or LGMW. A timely diagnosis was performed in five patients with presymptomatic hyperCKaemia, but two had already manifested with relevant changes on muscle morphology and MRI. Consequently, enzyme replacement therapy was started in 14/17 patients, including the 2 patients still clinically presymptomatic but with a laboratory evidence of disease progression.

Treatment of resistant insomnia and major depression.

Daily rhythms regulate everiday life and sleep/wake alternation is the best expression of this. Disruptions in biological rhythms is strongly associated with mood disorders, often being the major feature of this, major depressive disorder first of all. Although stabilization of rhythms produced by treatments have important outcome on therapeutic efficacy, insomnia often remains an unresolved symptom when major depression has otherwise been successfully treated with antidepressant. We review scientific literature in order to better clarify how to better approach insomnia as a clinical aspect to investigate and to early treat while treating other psychiatric conditions, major depression in particular. Insomnia is associated with impaired quality of life. It can be resolved with adequate diagnosis and treatment: it should be considered a comorbid condition and should be early identificated and treated in a multidisciplinary way, so that the ideal of treatment for patients with treatment resistant insomnia in major depression is an integration of non-pharmacologic measures, along with judicious use of medication, often used as an adjunctive therapy.

Treatment-resistant insomnia treated with pregabalin.

We report a case with refractory insomnia. We diagnosed her case as depression with high levels of anxiety, weakness, with diminished ability to think or concentrate and with a sensory-motor disorder. Although this last symptom was very distressing, it did not satisfy the criteria for RLS (Restless Legs Syndrome). After treatment with paroxetine (20 mg) and zolpidem (10 mg), anxiety and mood deflection were attenuated. Nevertheless, a mild depression, an intermittent awakening (fragmentation of the sleep-wake rhythm) and subsyndromal RLS persisted. Her resistant insomnia was treated with benzodiazepine sleeping drugs (triazolam 0.25 mg, lorazepam 2.5 mg, fluorazepam 30 mg) with only partial insomnia remission, antidepressants (trazodone 150 mg RP, mirtazapine 15-30 mg, agomelatine 50 mg) and antipsychotics (levomepromazine 25 mg, zuclopentixol 25 mg) without results. Her intractable insomnia was markedly responsive to pregabalin without side effects. Our hypothesis is that the therapy with pregabalin may be indicated for resistant insomnia associated with subsyndromal RLS, even when the latter does not satisfy fully all the criteria for diagnosis.

Nerve growth factor and brain-derived neurotrophic factor concentrations in schizophrenia: a review.

There is growing interest in the role of neurotrophins in the pathophysiology of schizophrenia. Neurotrophins are a large family of dimeric polypeptides that promote the growth and the differentiation of developing neurons in the central and peripheral nervous systems as well as the survival of neuronal cells in response to stress. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) concentrations are here reviewed in relation to medication-naive early psychotic patients and in medicated chronic schizophrenic patients. Most data point to decreased plasma and serum NGF and BDNF concentrations in naive drug and in medicated schizophrenic patients compared to healthy controls. Higher BDNF levels were observed in patients with the paranoid subtype of schizophrenia. Low serum BDNF levels were associated with reduction in hippocampal volume (HV) at the onset of schizophrenia. Evidence on the correlation between BDNF levels and positive and negative schizophrenic symptoms were ambiguous. There are contrasting results on a possible correlation between increase in BDNF concentrations and treatment with antipsychotics. Antipsychotic treatment can elevate NGF values, specifically atypical. Growth factors might be good candidates as prognostically and diagnostically useful markers in schizophrenia.

Observational clinical study in juvenile-adult glycogenosis type 2 patients undergoing enzyme replacement therapy for up to 4 years.

The objective of this study was to describe a large Italian cohort of patients with late-onset glycogen storage disease type 2 (GSDII) at various stages of disease progression and to evaluate the clinical effectiveness of alglucosidase alpha enzyme replacement therapy (ERT). Previous studies showed in late-onset patients ERT efficacy against placebo and variable response in uncontrolled studies. Seventy-four juvenile or adult GSDII patients were treated with ERT in a multicenter open label, non-randomized study, from 12 months up to 54 months. Recombinant human alpha glucosidase (rh-GAA) was injected by intravenous route at 20 mg/kg every second week. Patients were divided into three groups according to ERT duration: Group A received treatment for 12-23 months (n = 16), Group B for 24-35 months (n = 14), and Group C for more than 36 months (n = 44). Clinical assessment included a 6-min walk test (6MWT), forced vital capacity (FVC), the Walton and Gardner-Medwin score, the number of hours of ventilation, body mass index, echocardiography and blood creatine kinase (CK). Included in our cohort were 33 males and 41 females (M:F = 0.8:1), with a mean age at first symptoms of 28.3 years (range 2-55 years) and a mean age of 43 years at study entry (range 7-72 years). Seven wheelchair bound patients, as well as 27 patients requiring ventilation support, were included. After treatment we could observe an increase in distance walked on the 6MWT in the large majority of patients (48/58; 83%), with an overall mean increase of 63 m (from 320 ± 161 to 383 ± 178 m). After treatment in the majority of patients FVC was improved or unchanged (45/69; 65%). In ventilated patients we observed an improvement in average number of hours off the ventilator (from 15.6 to 12.1 h). Six patients stopped mechanical ventilation and two others started it. The effect of therapy was not related to ERT duration. Nine of 64 patients (13%) that underwent to echocardiography showed a variable degree of cardiac hypertrophy (left ventriculum or septum), and a positive effect was observed after 36 months of ERT in one adult case. Discontinuation of treatment occurred in four patients: one drop-off case, one patient died for a sepsis after 34 months of treatment and two patients stopped ERT for worsening of general clinical condition. Mild adverse effects were observed in four cases (5%). This study represents the largest cohort of late-onset GSDII patients treated with ERT, and confirm a positive effect of treatment. These results, obtained in a large case series on therapy, indicate a favourable effect of ERT therapy, even in more advanced stage of the disease.

Major depressive disorder, anhedonia and agomelatine: an open-label study.

Despite a wide range of available antidepressants, the effect of the treatment is often suboptimal and there is a need for more effective and better tolerated drugs. Unlike other antidepressants, agomelatine represents a new approach to depression with an innovative mechanism of action. It is an agonist of melatoninergic receptors MT1 and MT2 and a selective antagonist of 5-HT2c receptors. In this open-label 8-week study we aimed to investigate the efficacy of agomelatine on depressive symptoms in patients with major depression. Secondary endpoints were the effect of agomelatine on anhedonia. Thirty major depressive patients received a flexible dose (25-50 mg; per os, daily) of agomelatine. Depressive (Hamilton Depression Scale) and anxious (Hamilton Anxiety Scale) symptoms, anhedonia (Snaith Hamilton Rating Scale), and sleep quality (Leeds Sleep Evaluation Questionnaire) were assessed. Twenty-four patients (80%) completed 8 weeks of treatment. Significant improvements were seen at all visits on the HAM-D (p<.05), HAM-A(p<.01), SHAPS (p<.05), LSEQ (p<.05). Nine subjects (30%) were responders and 5 (17%) remitters at week 1; 18 (60%) were remitters by the end of the trial. There was no serious adverse event. No aminotrasferase elevations were noted. In line with previous studies, in which agomelatine was associated with early clinical improvement, this study also provides evidence of an early response and the findings of improvements in depression scores. Moreover, this is the first study where agomelatine was effective in the treatment of anhedonia. Additional trials are needed to delineate the place of agomelatine in the contemporary pharmacotherapy for depressive disorders.

Sleep disturbances in eating disorders: a review.

Psychiatric disorders are frequently associated with disturbances of sleep and circadian rhythms. This review focus on the relationship between sleep disturbances and eating disorders. In the first part are discussed the presence of sleep disorders among patients suffering from anorexia nervosa and bulimia nervosa, the macrostructure and microstructure of theirs sleep, the differences between the various subtypes in ED patients, the dreams of eating disordered patients and their recurrent contents. In the second part, there are treated sleep disturbances in binge eating disorder and other eating disorders not otherwise specified, such as nocturnal (night) eating syndrome and sleep-related eating disorder. In the third part, there are presented data concerning the neurobiological and neuroendocrinological correlates between feeding, metabolism, weight restoration and the processes regulating sleep. In conclusion, possible future investigations are proposed.

Inhibition of prostaglandin synthesis reduces the induction of MyoD expression in rat soleus muscle.

MyoD is a myogenic regulatory factor with a critical role in skeletal muscle development and regeneration. As muscle regeneration comes with an inflammatory process, it has been proposed that the inflammatory cells can play an important role in the induction of muscle fibres regeneration. The aim of the present work was to verify if a cyclooxygenase inhibitory drug (ketoprofen) would alter the normal expression of MyoD in a regenerating rat soleus muscle after an over-load lesion. Using immunohistochemical techniques, the numbers of m-cadherin-positive cells, a selective marker of satellite cells, and MyoD-positive cells were evaluated in functionally overloaded rat soleus muscles 4 days after a gastrocnemius tendon cut. The same study was conducted either with four rats injected with ketoprofen (100 mg/kg b.w./day) or with four rats injected with saline solution. The data obtained showed a very large decrease in the number of MyoD positive/m-cadherin positive cells in the ketoprofen injected group compared to the control group. Although further studies are needed to elucidate the sequence of biochemical events that induce a reduction of MyoD expression due to ketoprofen, the results demonstrate that prostaglandin synthesis is required for the induction of MyoD expression and that ketoprofen can affect this expression, with possible adverse effects on muscle regeneration.

Factor analysis of transesterification reaction of waste oil for biodiesel production.

In the present paper a factor analysis is presented for the enzymatic transesterification of waste oil for biodiesel production. The experimental data on batch reactor evidence two key variables: enzyme loading and mixing conditions. These variables were subjected to a factor analysis and their combined effect on the reaction performance was determined. Response surface methodology (RSM) was used based on a linear first order model (steepest ascent method) and on a second order one in proximity of the optimal solution. The result was a model able to predict reaction performance within the range of mixing rates and enzyme amount considered for model formulation and outside of it, as shown in the final validation. Best performances were obtained at high stirring and high enzyme loading.

Autonomic neuropathy in mixed cryoglobulinemia.

A retrospective, cross-sectional study was performed on a series of HCV-related mixed cryoglobulinemia (HCV-MC) patients to assess autonomic neuropathy (AN) and its relation to peripheral neuropathy (PN). Thirty consecutive patients affected by HCV-MC underwent clinical, neurological and electrodiagnostic examinations. Autonomic nervous system (ANS) involvement was assessed by functional cardiovascular tests and sympathetic skin response (SSR) evaluation. Sural nerve biopsy was performed in 10 patients with PN. All patients received steroids, 15 also received recombinant interferon-alpha2b (RIfn-alpha2b). PN occurred in 27 patients (90.0%) and AN in 4 (13.3 %) all with signs of PN. SSR was the autonomic test more frequently altered. Biopsy disclosed axonal degeneration more evident in the 4 patients with AN. Three out of 4 patients with AN received steroids and rIFN-alpha2b and 1 steroids alone. In our study on HCV-MC, it was concluded that AN can occur also without dysautonomic symptoms, SSR appears to be one of the optional tests to use together with dysautonomic tests to identify AN and finally PN and AN do not seem to be positively influenced by addition of rIFN-alpha2b to steroid treatment.

Primary cerebral toxoplasmosis: a rare case of ventriculitis and hydrocephalus in AIDS.

We describe the clinical, radiological and neuropathological findings in an adult AIDS patient presenting with ventriculitis and hydrocephalus as the primary manifestations of cerebral toxoplasmosis. Clinical symptoms including fever, headache, changes in mental status and focal neurological deficits were non-specific. Cranial computed tomography showed a subtile ventricular dilatation whereas magnetic resonance imaging disclosed triventricular hydrocephalus due to stenosis of the aqueduct and a periventricular nodular rim of high signal intensity on T2- and proton density-weighted images. This rim also showed a slight enhancement on post-contrast T1-weighted images. Focal intracerebral lesions could not be delineated, neither by neuroimaging nor by pathology. Neuropathological examination showed severe ventriculitis with large ependymal and subependymal necrosis as well as dilatation of the lateral and the third ventricle. The only microorganism demonstrated at histology in the central nervous system was Toxoplasma gondii. We conclude that ventriculitis and hydrocephalus without any focal parenchymal lesion may be the only manifestations of CNS toxoplasmosis. It is important to recognize this unusual form of presentation of cerebral toxoplasmosis in order to perform specific therapy.

Human mesenchymal stem cells are tolerized by mice and improve skin and spinal cord injuries.

INTRODUCTION: We sought to use human mesenchymal stem cells (HMSC) for skin and spinal cord repair in mice. MATERIALS AND METHODS: Human bone marrow obtained from a young healthy donor was used to separate and culture human mesenchymal stem cells (HMSC). Ten mice were included in each of four groups. A full-thickness skin defect was surgically performed on all mice in groups 1 and 2. A transverse complete medullar section was performed in groups 3 and 4. Groups 1 and 3 received HMSC IV infusion and local HMSC polymer implant. Groups 2 and 4 received only the IV HMSC infusion. Five control animals from each group went through the same lesions but they didn't receive treatment. RESULTS: After local administration of HMSC into the fibrin polymer combined with the IV infusion of HMSC, there was no immune rejection; all skin defects healed without scar or retraction at a median time of 14 days. Sixty percent of the animals treated with IV infusion and polymer with HMSC simultaneously had improved neurological activities, while all control mice with spinal cord injury experiments died or perpetuated their paralysis with worsening muscular atrophy and increasing propensity to skin damage. CONCLUSIONS: HMSC are not immunologically reactive and can trespass species defense barriers. Animals treated with these cells repaired injuries better than controls. In this way we propose that universal HMSC from donors can be cultured, expanded, and cryopreserved to be used in human organ or tissue regeneration.

Peripheral nervous system involvement in Klippel-Trenaunay syndrome.

Klippel-Trenaunay syndrome (KTS) is a rare congenital malformation of unknown etiology characterized by cutaneous hemangiomas, venous varicosities and bony and soft tissues hypertrophy usually affecting one limb. Several complex anomalies involving various organs and systems have been described, whereas involvement of the peripheral nervous system has rarely been reported in KTS. We describe the case of a 67-year-old woman with KTS and peripheral neuropathy related to the presence of epineurial microscopic arteriovenous anastomoses (AVA) and endoneurial vascular coils in sural nerve biopsy from both hypertrophic and non-hypertrophic limb. The maintenance of AVA has been proposed to be the cause of the hypertrophy. The observation in our patient of AVA in non-hypertrophic limb contrasts with this hypothesis.

Improvement of chronic idiopathic urticaria with L-thyroxine: a new TSH role in immune response?

BACKGROUND: The association between chronic idiopathic urticaria (CIU) and autoimmune thyroiditis (AT) is known, as well as major prevalence of antithyroid antibodies in the allergical subjects and other autoimmune diseases. We have evaluated the effects of l-thyroxine on clinical symptoms of CIU in AT patients suggesting the hypothesis of a new thyroid-stimulating hormone (TSH) role in immune system. METHODS: In 20 female patients with CIU + AT, both hypothyroid and euthyroid, we have investigated the therapeutic effects of l-thyroxine dosed to suppress the TSH. Free-T3, Free-T4, TSH, antithyroperoxidase and antithyroglobulin antibodies, total immunoglobulin (Ig)E, Rheuma test and eritro-sedimentation rate were monitored during treatment. RESULTS: In 16 patients a strong decrease of urticaria symptoms has happened after 12 weeks. The TPO Ab and HTG Ab clearly decreased in 14 patients. Furthermore, in two patients with rheumatoid arthritis and in two patients with pollen allergy a strong decrease of rheuma test titer and total IgE has happened. CONCLUSION: The reason of AT is associated to CIU and others allergical and autoimmune diseases is poorly known. The exclusive hormonal therapy reduces the symptoms of CIU and inflammatory response in many chronic diseases associated to AT. We suggest a stimulatory effect of TSH able to produce considerable changes of the immune response and immune tolerance in patients with AT causing target organs damage. The causal mechanism involves immune, nervous and endocrine system, sharing a common set of hormones, cytokines and receptors, in a unique totally integrated loop (the neuro-immuno-endocrine axis).

Cirugía fetal experimental en un modelo animal para la corrección de mielomeningocele / Experimental fetal surgery in an animal model for the correction of myelomeningocele

Introducción. El mielomeningocele representa una de las malformaciones congénitas más frecuentes y severas en humanos, que afecta aproximadamente a 1 de cada 2.000 recién nacidos en el mundo. Tiene una enorme significación médica y social, por la importante morbilidad a que se asocia, con gran cantidad de secuelas y un elevado coste en salud. Existe sólida evidencia que apoya la necesidad de tratamiento precoz. Dentro de las posibilidades de tratamiento actuales tiene especial interés la reparación quirúrgica durante la vida intrauterina. El trabajo con un modelo animal constituye el paso previo necesario a la intervención en humanos. Objetivos. En concordancia con otros grupos de investigadores, hemos elegido un modelo animal que permita conocer los resultados de la reparación de la columna vertebral en mielomenigoceles creados instrumentalmente. Material y métodos. Durante el período de mayo de 2002 hasta mayo de 2004 se ha reclutado un grupo de 23 ovejas de raza merina a las que se les realizó quirúrgicamente, a los 80 días de preñez, un mielomeningocele, realizando una laminectomía lumbar de 1 a 4 con apertura del canal medular y exposición del contenido al líquido amniótico. Las ovejas fueron aleatorizadas para ser incluidas en tres grupos: un grupo control y dos grupos de intervención. En uno de ellos se realizó una reparación neuroquirúrgica convencional y en el otro grupo se realizó una reparación colocando una membrana de tejido dérmico porcino acelular cultivado. Resultados. Los corderos del grupo control nacieron con manifestaciones clínicas severas de la enfermedad (tres de cinco corderos), con incapacidad en la deambulación e incontinencia de esfínteres; en los corderos de ambos grupos de intervención las manifestaciones clínicas de espina bífida fueron leves (cuatro de cinco corderos), con dificultad leve en la deambulación y continencia de esfínteres. Conclusiones. Los resultados alcanzados por el trabajo, debido al reducido número de intervenciones, no son concluyentes, pero muestran una tendencia a favor de la intervención de reparación intraútero del mielomeningocele. Las consecuencias de estos resultados en la práctica clínica deberán ser observadas a la luz de los resultados del Management of Myelomeningocele Study (MOMS) que se desarrolla actualmente en Estados Unidos en cuatro centros. Comentario final. La realización del presente trabajo ha tenido enorme significación para los autores ya que se ha reunido un equipo multidisciplinario que incluye anestesiólogos, neurocirujanos, neonatólogos, obstetras, veterinarios, enfermeros, neurólogos, etc., y se ha alcanzado el objetivo de adquirir nuevas destrezas que serán fundamentales para el manejo futuro de la cirugía fetal intraútero (AU)

Introduction. Myelomeningocele is one of the most frequent and severe congenital defects in humans, affecting approximately one in 2000 worldwide. This pathology is of great medical and social relevance due to its high morbidity, multiple sequela and high social cost. There is supporting evidence in favor of early treatment, particularly through intra uterine surgical correction. The work on animal models is a required preliminary step before intervention on humans. Objectives. In agreement with several other investigative groups we have chosen an animal model that allows us to know the results of spine correction in surgically induced myelomeningocele. Material and methods. Between may of 2002 and may of 2004 we recruited 23 sheep on which we induced myelomeningocele surgically at 80 days of gestational age, through 1 to 4 lumbar laminectomy with opening of bone marrow channel and exposure to amniotic fluid. AH sheep were randomized to be included in three groups: control group A, and intervention groups B (conventional intervention) and C (conventional plus noncellular porcine skin patch. Results. Neonate lambs (three out of five) in the control group presented with severe clinical disease related disabilities, namely walking impairment and incontinence. Lambs in B and C groups showed less severe impairment: slight walking handicap and lack of incontinence. Conclusions. Owing to the small sampling the results we reached are not conclusive, though they show a trend in favor of intrauterine correction of myelomeningocele. Relevance of these findings should be availed for clinical practice through the results from Management of Myelomeningocele Study (MOMS), currently ongoing in four UScenters. Final comment. The present trial represents an important advance for all participants in that it gathered a multidisciplinary team composed of anesthesiologists, neurosurgeons, pediatric neurosurgeons, obstetricians, pediatricians, vets, nurses, etc., and has led us to the acquisition of essential handskills for the future management of intra uterine fetal surgery (AU)