ABSTRACT
OBJECTIVES: Periventricular nodular heterotopia (PNH) is a malformation of cortical development which presents with heterogeneous imaging, neurological phenotype and outcome. There is a paucity of comprehensive description detailing the prenatal diagnosis of PNH. The aim of this study is to report neuroimaging features and correlated outcomes in order to delineate the spectrum of prenatally diagnosed PNH. METHODS: It was a retrospective study over 15 years in five tertiary centers. All fetuses with prenatally diagnosed PNH were collected. Fetal ultrasound and MRI were reviewed and genetic screening collected. Prenatal findings were analyzed in correlation to fetopathological analyses and post-natal follow up. RESULTS: Thirty fetuses (22 females and 8 males) with PNH were identified. The two major ultrasound signs were ventriculomegaly associated with dysmorphic frontal horns (60%) and posterior fossa anomalies (73.3%). On MRI, two groups of PNH were identified: the contiguous and diffuse PNH (nâ¯=â¯15, 50%), often associated with megacisterna magna, and the non-diffuse, either anterior, posterior or unilateral PNH. FLNA mutations were found in 6/11 cases with diffuse PNH. Additional cortical malformations were exclusively observed in non diffuse PNH (9/15; 60%). Twenty-four pregnancies (80%) were terminated. Six children aged 6 months to 5 years are alive. Five have normal neurodevelopment (all had diffuse PNH) whereas one case with non diffuse PNH has developmental delay and epilepsy. CONCLUSION: PNH is heterogeneous but patients with diffuse PNH are a common subgroup with specific findings on prenatal imaging and implications for prenatal counseling.
Subject(s)
Brain/diagnostic imaging , Epilepsy/diagnosis , Periventricular Nodular Heterotopia/genetics , Prenatal Diagnosis , Brain/physiopathology , Child , Child, Preschool , Epilepsy/diagnostic imaging , Epilepsy/genetics , Epilepsy/physiopathology , Female , Humans , Infant , Magnetic Resonance Imaging , Male , Periventricular Nodular Heterotopia/diagnosis , Periventricular Nodular Heterotopia/diagnostic imaging , Periventricular Nodular Heterotopia/physiopathology , Phenotype , Pregnancy , Retrospective StudiesABSTRACT
Silver nanoparticles (AgNPs) are widely used in industrial and medical applications and humans may be exposed through different routes, increasing the risk of toxicity. We investigated the transcript expression of genes involved in the regulation of the hypothalamic-pituitary-testicular (HPT) axis and the parameters associated with sperm functionality after prepubertal exposure. AgNPs modulated the transcript expression of genes involved in the control of the HPT axis and spermatogenesis in the groups treated with lower doses, while the functional parameters related to sperm and puberty were affected in the groups administered higher doses. These results suggest that the HPT axis is disrupted by AgNPs during the prepubertal and pubertal periods, which are highly susceptible windows for the endocrine-disrupting chemical activity.
ABSTRACT
Portable devices are commonly used at bedside in everyday practice. Transplant procurement coordinators routinely have to deal with protocols and flow charts and need to assess the donor condition several times. In our experience, a great part of the organ procurement management work is provided by nurses "on call." We developed an application for iOS devices to facilitate their approach to relatives and procedures for organ donation. The application, which includes algorithms, tutorials, and simple calculators, has been designed by transplant procurement coordinators to speed up the process of organ donation and at the same time to be as accurate as possible for the process. It can be used alongside all of the procedures for procurement in the emergency room, intensive care unit, operating room, and morgue in both brainstem-dead and cadaver organ donors. The application could be effective in organ procurement management for everyday practice.
Subject(s)
Mobile Applications , Tissue and Organ Procurement , Efficiency, Organizational , Humans , Tissue DonorsABSTRACT
In 2010-2011, we used FMECA to prospectively assess risk-management in chemotherapy of children with cancer, in a third level Italian children's Hospital (Ospedale Pediatrico Bambino Gesù; OPBG). We designed a flow chart representing the entire process; we described potential failure points for each step of the process, as well as their potential underlying causes. We calculated the risk priority number (RPN) of each failure point based on the severity of the failure, the frequency of occurrence, and the likelihood of detecting the failure prior to completion of the process. All FMECA activities were supported by a web-based tool. The highest RPN values were observed for failure points of the paper-based chemotherapy medication orders sent from clinicians to Pharmacy, the transcription of the orders into the Pharmacy paper-based work-sheet for medication preparation, and the selection of medications to be used for chemotherapy preparation. Causes of these failures were mostly related to illegible or incomplete handwriting. As a consequence of these results, the implementation of an electronic ordering process for children's chemotherapy medications was proposed as risk-reducing action.
Subject(s)
Antineoplastic Agents/adverse effects , Neoplasms/drug therapy , Child , Humans , Risk Assessment/methods , Risk Assessment/standardsABSTRACT
Muir Torre syndrome is a rare autosomal dominant cancer-predisposing syndrome characterized by the occurrence of sebaceous gland neoplasms and/or keratoacanthomas associated with visceral malignancies that belong to the spectrum of hereditary non polyposis colorectal cancer (HNPCC), i.e., tumors of gastrointestinal and genitourinary tracts. Hepatobiliary malignancy in association with Muir Torre syndrome has rarely been reported. Here, we describe a case of Muir Torre syndrome associated with an hepatocellular-carcinoma in a patient with a non-cirrhotic liver and an HNPCC-family with multiple cases of hepatocellular carcinoma.
Subject(s)
Carcinoma, Hepatocellular/diagnosis , Liver Neoplasms/diagnosis , Muir-Torre Syndrome/pathology , Neoplasms, Multiple Primary/diagnosis , Skin Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/therapy , Female , Humans , Liver Neoplasms/therapy , Male , Middle Aged , Muir-Torre Syndrome/therapy , Neoplasms, Multiple Primary/therapy , Pedigree , Prognosis , Skin Neoplasms/therapyABSTRACT
The results of the Randomized Aldactone Evaluation Study (RALES) and of several experimental studies have indicated that excess aldosterone detrimentally affects cardiovascular morbidity and mortality by acting through both classical and non-classical mineralocorticoid receptors. The effects mediated through classical mineralocorticoid receptors entail enhanced sodium and water reabsorption, potassium loss and hypokalaemia, congestion, increased vascular resistance and hypertension. Those occurring through non-classical mineralocorticoid receptors located on myofibroblasts comprise cardiac hypertrophy and fibrosis, which may be due to a direct effect of aldosterone on collagen synthesis. Data obtained in primary aldosteronism patients demonstrated left ventricular hypertrophy, as well as changes in left ventricular filling that can be accounted for by cardiac fibrosis. Available clinical data indicate that in a considerable proportion of congestive heart failure (CHF) patients treated with angiotensin converting enzyme (ACE) inhibitors, aldosterone secretion can escape from blockade of the renin-angiotensin system, thus suggesting that additional mechanisms, besides angiotensin II, can play an important role in the regulation of aldosterone secretion. Compelling evidence indicates that endothelin (ET)-1 is overtly increased in severe CHF and thus is a likely candidate for the aldosterone 'escape' phenomenon in CHF. Endothelin-1 is expressed in the adrenal cortex, together with its receptor subtypes A (ETA) and B (ETB), and directly stimulates aldosterone secretion in different species, in humans by acting via both ETA and ETB receptor subtypes. Moreover, we have recently found that the novel endothelin peptide ET-1 (1-31), by acting as an ETA agonist, can also be involved in the regulation of growth of the adrenal cortex, as well as in the pathogenesis of Conn's adenoma. In this paper, we review the findings suggesting a relationship between activation of the ET-1 system, enhanced aldosterone secretion and cardiac fibrosis and discuss the implications of endothelin antagonism for cardiovascular disease.
Subject(s)
Aldosterone/metabolism , Cardiovascular Diseases/metabolism , Endothelin-1/metabolism , Mineralocorticoid Receptor Antagonists/therapeutic use , Spironolactone/therapeutic use , Adrenal Cortex/drug effects , Adrenal Cortex/growth & development , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Cardiovascular Diseases/drug therapy , Clinical Trials as Topic , Collagen/biosynthesis , Endothelin Receptor Antagonists , Endothelin-1/drug effects , Endothelins/metabolism , Heart Failure/drug therapy , Heart Failure/metabolism , Humans , Morbidity , Randomized Controlled Trials as Topic , Receptor, Endothelin A , Receptor, Endothelin B , Renin-Angiotensin System/drug effectsABSTRACT
The yema gene region of Drosophila melanogaster is a cluster of maternally acting genes isolated in differential screens. At least ten transcripts are encoded by the yema gene region; most of them are produced by independent transcription units (eight different transcription units). Using RNA dot-blot analysis and in situ hybridization to tissue sections, we have realized a comprehensive survey of the temporal and spatial expression of the yema transcripts. All these transcripts are maternally expressed. Five of them display a strict maternal expression. They are found exclusively in the female germ line (nurse cells and oocyte). These transcripts are still present in the embryo as maternal information. However, a subset of the yema genes also shows an embryonic and a post-embryonic expression. Interestingly, this expression is essentially restricted to the central nervous system (CNS) throughout the fly development, to the larval and pupal imaginal discs and to a subset of cells in the male gonad, the spermatocytes. Strikingly, these expression sites mainly contain proliferating and/or differentiating cells.
Subject(s)
Drosophila melanogaster/genetics , Animals , Cell Differentiation/genetics , Cell Division/genetics , Central Nervous System/embryology , Cloning, Molecular , Drosophila melanogaster/embryology , Gene Expression Regulation/physiology , Male , Multigene Family/genetics , Multigene Family/physiology , RNA/metabolism , Spermatocytes/metabolism , Time Factors , Transcription, GeneticABSTRACT
We report an application of the random primer labeling technique to in situ hybridizations on tissue sections. The ease of the method and the high specific activity achieved make it valuable when a large number of probes must be analyzed and high sensitivity is needed. We have applied this technique to study the spatial expression of a cluster of maternally acting genes (the yema gene region of Drosophila melanogaster which encodes eleven transcripts, some of them having a very low level of expression) (Aït-Ahmed et al., 1978: Dev Biol 122:153; Aït-Ahmed et al., unpublished results). The results reported here concern one of the transcripts of the yema region, which displays a peculiar anterior localization in the oocyte. We demonstrate that the "oligo-labeling" method allows a far better level of detection of the transcript of interest.
Subject(s)
DNA/genetics , Multigene Family , Nucleic Acid Hybridization , Oligonucleotides , Animals , Autoradiography , Drosophila melanogaster , Female , Gene Expression Regulation , Predictive Value of Tests , Protein Biosynthesis , Transcription, GeneticABSTRACT
We used a molecular approach to search for maternally expressed genes in Drosophila melanogaster. The relative merits of differential and competition screens were analyzed in a series of reconstruction experiments using either purified phage plaques or derivative DNA sequences. In the course of this study, we isolated 5 clones whose RNA level varies during early embryogenesis. Three gastrula differential clones, b4, b8 and d3, are present in numerous copies in the genome; clone b4 hybridizes with the copia-like B104 repetitive sequence described by Scherer et al. We also isolated 2 maternally-expressed genes, not previously identified in either classical genetic or similarly molecular-based screens. These clones, b11 and d6, map at cytogenetic positions 98F and 4F respectively, on the polytene chromosome map.
Subject(s)
Drosophila melanogaster/genetics , Genes , RNA/genetics , Animals , Chromosome Mapping , Cloning, Molecular , DNA/analysis , DNA/genetics , Drosophila melanogaster/embryology , Gastrula/physiology , Gene Expression Regulation , Nucleic Acid Hybridization , RNA/analysis , Repetitive Sequences, Nucleic Acid , Transcription, GeneticABSTRACT
We have characterized a genomic clone of Drosophila melanogaster which codes for four transcripts that are synthesized during oogenesis, remain abundant in the preblastoderm embryo, and then vanish during gastrulation. One of the transcripts varies in concentration along the anterior-posterior axis of the oocyte. This cluster of maternally acting genes (yema) maps to 98 F3-10 on chromosome arm 3 R.
Subject(s)
Drosophila melanogaster/genetics , Genes , Animals , Chromosome Mapping , DNA, Recombinant/isolation & purification , Drosophila melanogaster/embryology , Female , Male , Nucleic Acid Hybridization , Oogenesis , Poly A/genetics , RNA/genetics , RNA, Messenger , Transcription, GeneticABSTRACT
To evaluate the usefulness of urinary cyclic AMP (U-cAMP) expressed as nmol/100 ml glomerulus filtrate (GF) when discriminating various hypercalcemic states, we studied 99 patients. Patients with primary hyperparathyroidism (PHPT) showed a positive correlation between individual S-calcium levels and U-cAMP, nmol/100 ml GF (females r=0.49, n=40, p less than 0.01 and males r=0.91, n=7 p less than 0.001). There was also a correlation between U-cAMP, nmol/100 ml GF, and the weight of the adenomas (females r=0.36, n=32, p less than 0.05) and males r=0.79, n=6, p less than 0.05). Patients with PHPT and normal renal function excreted more U-cAMP than controls, 6.0 +/- 1.6 versus 4.3 +/- 1.0 nmol/100 ml GF (mean +/- SD). Of 47 patients with PHPT and normal renal function, 29 showed values below the upper normal limit, 6.3 nmol/100 ml GF (mean +/-2 SD), of the control group; the overlap was 62%. When U-cAMP was expressed as mumol/24 hours, the overlap was 40/47 (85%) and, when expressed as mumol/g creatinine, 31/47 (66%). Three patients with sarcoidosis and two with malignancies and hypercalcemia showed excretory values of U-cAMP, nmol/100 ml GF, above the upper normal limit. Patients with acromegaly or prolactinoma showed normal values of U-cAMP, nmol/100 ml GF. The present data indicate that all three types of determinations of urinary cAMP based on 24 hour urine collections are of little value in the differential diagnosis of hypercalcemic states.