Long-term outcomes of children with umbilical vein varix diagnosed prenatally.

OBJECTIVES: The current study aims were to assess the long-term outcomes of children who were diagnosed with umbilical vein varix (UVV) prenatally. METHODS: The study included fetuses with UVV diagnosed in the community between the years 2005 and 2011. They all have been refereed to our Ultrasound Unit for diagnosis' confirmation. This has been conducted locally by a single operator. After delivery, they were matched by gestational age at birth with a set of newborns from a random list. Developmental delay was assessed by telephone interview using a questionnaire based on Ages and Stages Questionnaire. If the child's score (both in the study and control group) was below the cut-off in one or more domain(s), the families were offered an examination by a child developmental health care team. RESULTS: There was no perinatal mortality in both groups. A low-development score was found in 41.7% (15/36) and 3.7% (4/108) in UVV and control group, respectively (P < 0.05). In 10 out of 15 (67%) children in the UVV group with low scores, formal developmental assessment was performed. Four (40%) were diagnosed having developmental delay. Among the four controls with low score, two families refused additional assessment and one child died. The remaining child was found to have normal development. CONCLUSIONS: A possible association between UVV diagnosed prenatally and child developmental delay was found. However, the clinical implications of these findings are still premature; thus, additional studies are needed.

[Selective mutism].

Selective mutism is an uncommon disorder in young children, in which they selectively don't speak in certain social situations, while being capable of speaking easily in other social situations. Many etiologies were proposed for selective mutism including psychodynamic, behavioral and familial etc. A developmental etiology that includes insights from all the above is gaining support. Accordingly, mild language impairment in a child with an anxiety trait may be at the root of developing selective mutism. The behavior will be reinforced by an avoidant pattern in the family. Early treatment and followup for children with selective mutism is important. The treatment includes non-pharmacological therapy (psychodynamic, behavioral and familial) and pharmacologic therapy--mainly selective serotonin reuptake inhibitors (SSRI).

Experimental feasibility of multi-energy photon-counting K-edge imaging in pre-clinical computed tomography.

Theoretical considerations predicted the feasibility of K-edge x-ray computed tomography (CT) imaging using energy discriminating detectors with more than two energy bins. This technique enables material-specific imaging in CT, which in combination with high-Z element based contrast agents, opens up possibilities for new medical applications. In this paper, we present a CT system with energy detection capabilities, which was used to demonstrate the feasibility of quantitative K-edge CT imaging experimentally. A phantom was imaged containing PMMA, calcium-hydroxyapatite, water and two contrast agents based on iodine and gadolinium, respectively. Separate images of the attenuation by photoelectric absorption and Compton scattering were reconstructed from energy-resolved projection data using maximum-likelihood basis-component decomposition. The data analysis further enabled the display of images of the individual contrast agents and their concentrations, separated from the anatomical background. Measured concentrations of iodine and gadolinium were in good agreement with the actual concentrations. Prior to the tomographic measurements, the detector response functions for monochromatic illumination using synchrotron radiation were determined in the energy range 25 keV-60 keV. These data were used to calibrate the detector and derive a phenomenological model for the detector response and the energy bin sensitivities.

Universality and hysteretic dynamics in rapid fracture.

Experiments in the dynamic fracture of brittle polyacrylamide gels show that a single-crack state undergoes a hysteretic transition to the microbranching instability with a characteristic activation time. Quantitative measurements also indicate that features such as crack front inertia, self-focusing of microbranches, and the appearance of front waves are universal attributes of dynamic fracture.

Haemophilus influenza type b vaccine in Israel: experience in a paediatric ambulatory clinic.

In Israel, vaccination are the overall responsibility of the government. We were the first in Israel to give the Hib (Haemophilus influenza type b) vaccine to the population, through independent means, without government control. The aim of the study was to follow longitudinally the specific group of children vaccinated in our ambulatory clinic. In this study, 1,497 children between 2 and 52 [mean (SD) 13 (9)] months of age at the time of first vaccination were vaccinated with Hib vaccine. Over the next 7 years, they were followed up by repeated phone calls when parents were asked about hospitalisation and any serious infectious diseases. Of the 1,497, 1,444 were followed during the years 1992 to 1999 and 36 were hospitalised during this time. All blood and cerebrospinal fluid cultures were negative. No proven case of Hib infection could be demonstrated. Despite the small sample size, this study justifies the continued use of the vaccine along with maintaining surveillance for Hib infection.

Identification and localization of a thylakoid-bound carbonic anhydrase from the green algae Tetraedron minimum (Chlorophyta) and Chlamydomonas noctigama (Chlorophyta).

In order to broaden our understanding of the eukaryotic CO2-concentrating mechanism the occurrence and localization of a thylakoid-associated carbonic anhydrase (EC 4.2.1.1) were studied in the green algae Tetraedron minimum and Chlamydomonas noctigama. Both algae induce a CO2-concentrating mechanism when grown under limiting CO2 conditions. Using mass-spectrometric measurements of 18O exchange from doubly labelled CO2, the presence of a thylakoid-associated carbonic anhydrase was confirmed for both species. From purified thylakoid membranes, photosystem I (PSI), photosystem II (PSII) and the light-harvesting complex of the photosynthetic apparatus were isolated by mild detergent gel. The protein fractions were identified by 77 K fluorescence spectroscopy and immunological studies. A polypeptide was found to immunoreact with an antibody raised against thylakoid carbonic anhydrase (CAH3) from Chlamydomonas reinhardtii. It was found that this polypeptide was mainly associated with PSII, although a certain proportion was also connected to light harvesting complex II. This was confirmed by activity measurements of carbonic anhydrase in isolated bands extracted from the mild detergent gel. The thylakoid carbonic anhydrase isolated from T. minimum had an isoelectric point between 5.4 and 4.8. Together the results are consistent with the hypothesis that thylakoid carbonic anhydrase resides within the lumen where it is associated with the PSII complex.

Caspase activation by adenovirus e4orf4 protein is cell line specific and Is mediated by the death receptor pathway.

Adenovirus E4orf4 protein has been shown to induce transformed cell-specific, protein phosphatase 2A-dependent, and p53-independent apoptosis. It has been further reported that the E4orf4 apoptotic pathway is caspase-independent in CHO cells. Here, we show that E4orf4 induces caspase activation in the human cell lines H1299 and 293T. Caspase activation is required for apoptosis in 293T cells, but not in H1299 cells. Dominant negative mutants of caspase-8 and the death receptor adapter protein FADD/MORT1 inhibit E4orf4-induced apoptosis in 293T cells, suggesting that E4orf4 activates the death receptor pathway. Cytochrome c is released into the cytosol in E4orf4-expressing cells, but caspase-9 is not required for induction of apoptosis. Furthermore, E4orf4 induces accumulation of reactive oxygen species (ROS) in a caspase-8- and FADD/MORT1-dependent manner, and inhibition of ROS generation by 4,5-dihydroxy-1, 3-benzene-disulfonic acid (Tiron) inhibits E4orf4-induced apoptosis. Thus, our results demonstrate that E4orf4 engages the death receptor pathway to generate at least part of the molecular events required for E4orf4-induced apoptosis.

Imaging after urinary tract infection in male neonates.

OBJECTIVE: To assess the frequency of urinary tract anomalies in male neonates <8 weeks old who presented with urinary tract infection (UTI), and to evaluate a suitable imaging approach after the initial infection. DESIGN: During a period of 4.5 years, from July 1994 through December 1998, 45 male neonates <8 weeks old (range: 5-56 days; mean: 23.77 days) with UTI were hospitalized. All patients had an ultrasound (US) and a voiding cystourethrogram (VCUG), except 1 neonate in whom VCUG was unsuccessful because of technical problems. A dimercaptosuccinic acid (DMSA) scan was recommended to all patients but was performed only in 30 of 45, most of them with an abnormal VCUG. The renal scan was performed at least 4 months after the UTI. RESULTS: Urinary tract abnormalities were observed in 22 of 45 male neonates. Nineteen had vesicoureteral reflux (VUR), 1 had VUR and a double collecting system, 1 had VUR and a posterior urethral valve, and 1 had an ureteropelvic junction stricture. Renal atrophy or scars, as demonstrated by DMSA scan, were detected almost exclusively in neonates with VUR grade 3 and above. Only 1 neonate with VUR grade 1 had a pathologic DMSA, and the US of this male also demonstrated renal atrophy. Escherichia coli was the pathogen in 62% (28 of 45), and 9 boys had bacteremia. CONCLUSION: We suggest that US and VCUG should be performed routinely after the initial UTI in male neonates. Renal scan should be reserved for those cases in which the US suggests renal parenchymal damage or when VCUG detects VUR grade 3 and above.

The efficacy of oral deferiprone in acute iron poisoning.

Due to its high cost and need for parenteral administration, the standard iron chelator deferoxamine is not used in many individuals with acute and chronic iron poisoning worldwide. Deferiprone is the first oral iron chelator to be shown to be effective in chronically iron overloaded thalassemia patients. Its efficacy, by oral administration, in acute iron poisoning has not been tested. Our objective was to determine whether orally administered deferiprone can reduce the mortality of rats following acute, toxic, oral doses of iron. Rats were administered 612 mg/kg elemental iron orally, corresponding to LD50 in the species tested. Two other groups received the same oral dose of iron followed by oral deferiprone: 800 mg/kg and 800 mg/kg, followed by another dose of 800 mg/kg 2 hours later. Coadministration of 800 mg/kg deferiprone with the iron decreased mortality from 30% to 6.6% after 2 hours (P = .02), from 40% to 16.6% after 12 hours (P = .04), and from 53.3% to 20% after 24 hours (P = 0.007). Mortality was also significantly decreased among animals coadministrated 2 repeated doses of deferiprone of 800 mg/kg with iron, to 0%, 9%, and 18%, and 2, 12, and 24 hours postdrug administration, respectively (P = .04, .05, .04, respectively). Histologically, there was a dose-dependent decrease in iron accumulation in the gastrointestinal tract. Orally administered deferiprone can decrease morbidity and mortality caused by acute iron overdose in rats. Oral deferiprone holds promise in the treatment of iron poisoning in humans.

[Familial hemiplegic migraine of childhood].

Familial hemiplegic migraine is a rare autosomal, dominant, migraine subtype. It is characterized by acute episodes of hemiplegia and hemisensory deficits, and other neurological abnormalities occurring either before or together with severe headache, nausea and vomiting; episodes last several hours and then spontaneously subside. Intervals between episodes are relatively prolonged. Unless there is a relevant family history suggesting this syndrome, the diagnosis is usually delayed. Recently the gene for the syndrome was identified on chromosome 19. We report 3 boys and 1 girl, 11-15 years old with hemiplegic migraine.

Acute iron intoxication: significant differences between sexes.

Iron, one of the common medications in use among children and adults, is the leading cause of pediatric unintentional ingestion fatalities and is not an uncommon poisoning among adults. Accidental ingestion is common because iron-containing compounds are readily available, brightly colored, often sugar coated, and frequently considered harmless vitamins. There are no data on differences between sexes with regard to iron intoxication, and the management of iron overdose is the same for females and males. After oral administration by gavage of the LD50 of iron to Wistar rats, the pharmacokinetics of iron, baseline and peak serum iron levels, and mortality rates were compared between sexes. Prepubertal females died significantly more than males (p < 0.01), pubertal females died significantly earlier than males (p < 0.04), and the same was true among adult rats (p = 0.02). Baseline serum iron levels were not significantly different between prepubertal female and male rats, but female pubertal rats had significantly higher baseline iron levels than males (p = 0.006). After iron administration, females had significantly higher peak serum iron concentrations (p < 0.03). Mechanisms of iron absorption are still not completely known and, probably, there are differences in iron absorption between sexes, which may account for the differences in serum iron levels and mortality rates. While the therapeutic approach in cases of intoxication is individual, iron intoxication, as may be true for other poisonings also, treatments administered to females may need to be different from that given to males.

The effect of BCECF on intracellular pH of human platelets.

2',7'-Bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF) is frequently used for fluorometric determination of intracellular pH (pHi) and its metabolic changes. Studies of BCECF-loaded platelets have reported different pHi values in the range of 6.98 to 7.35, despite the use of the same probe. It is now shown that intracellular BCECF (BCECFi) content affects pHi, and that its over-loading, leads to significantly lower pHi. Different pHi values can be reproduced by changing BCECFi, as reflected by fluorescence intensity. The major loading factors are: the concentration of the probe parent compound, BCECF acetoxymethyl ester (AM), and whether this ester is partly hydrolyzed externally when applied in plasma. When least affected by BCECF, platelet pHi is 7.34. High BCECFi does not affect ATP content, buffer capacity, activation of Na+/H+ exchange by protein kinase C (PKC) and basal PKC activity. On the other hand high BCECFi does inhibit the Na+/H+ exchange rate by over 50%. Since the Na+/H+ exchange strongly affects platelets pHi, it is proposed that this inhibition accounts, at least partly, for the lowered pHi in BCECF over-loaded platelets.

Cyclic AMP-related and cation-affected human platelet chloride transport regulation.

Cystic fibrosis has been characterized as a defect in the regulation of cyclic AMP-dependent transepithelial chloride transport. The activation of cyclic AMP-dependent protein kinase A by cyclic AMP occurs normally in cystic fibrosis cells, but they fail to transport chloride ions in response to protein kinase A stimulation. Defective chloride secretion and abnormal electrolyte transport occurs in several organs including the lung, sweat glands, intestine and pancreas. The present work was aimed at exploring whether the same or similar regulatory systems are functional in platelets, and if they are altered or deficient in individuals with cystic fibrosis. Chloride transport in platelets from normal subjects and from cystic fibrosis patients was measured by cell sizing techniques where chloride permeability is the limiting factor. In platelets from healthy volunteers, the chloride channel blocker, 5-nitro-2-(3-phenylpropylamino) benzoic acid, inhibits the transport in a dose-dependent manner. The preservation of chloride transport capability is shown to be dependent upon the presence of either Ca2+ or two divalent cation substitutes, Cd2+ or Cu2+. It is also shown that in normal subjects 0.1 mumol/l prostaglandin E1, which elevates cyclic AMP 6 times and abolishes platelet aggregation, significantly enhances the rate constant of the transport. Furthermore, in five out of nine cystic fibrosis patients studied, platelet chloride transport did not respond to stimulation by prostaglandin E1.

42 kDa Protein as a Substrate for Protein Phosphatase (s) in Intact Human Blood Platelets.

The level of phosphorylation of any cellular protein depends on the balance of the activities of protein kinases and protein phosphatases that act on the protein. In this study, we have characterized, in intact human blood platelets, the activity of protein phosphatase (s) that reverse the action of protein kinase C (PKC), using as a substrate, endogenous 42 kDa protein which has been previously phosphorylated by PKC. In this study 1,2-dihexanoyl-sn-glycerol (DHG) was used to stimulate PKC, diacylglycerol kinase inhibitor-R59022 was used to maintain the activity of PKC and staurosporine and okadaic acid were used to inhibit PKC and protein phosphatases respectively. Our observations indicate that: (1) protein phosphatase 1 (PP1) and/or protein phosphatase 2A (PP2A) are likely to be the enzymes that reverse the phosphorylation activity of PKC on the 42 kDa protein; (2) PP1 and/or PP2A dephosphorylate sites which have been previously phosphorylated by PKC; and (3) PP1 and/or PP2A dephosphorylate, on the 42 kDa protein, both serine and threonine residues, which have been previously phosphorylated by PKC.