[Placental site trophoblastic tumor with atypical choriocarcinoma. Case Report]. / Tumor trofoblástico del sitio placentario con evolución a coriocarcinoma. Caso clínico.

BACKGROUND: The placental site trophoblastic tumor is the second rarest tumor of trophoblastic disease, with less than 300 cases reported. Clinical presentation it's a diagnostic challenge, it has an unpredictable malignant potential, and it can develop choriocarcinoma and even have simultaneous presentation. CASE REPORT: We present the case of a 34 year old woman with chronic transvaginal bleeding since her last cesarean (five months ago), with histologic diagnosis of placental site trophoblastic tumor and inmuno- histoquimic report of choriocarcinoma, this early diagnosis improves her survival prognostic. CONCLUSION: placental site trophoblastic tumor and their evolution to choriocarcinoma have a low rate but it's possible. That it's the reason why complete diagnosis with biopsy, histologic and inmunohistoquimic report is mandatory to improve therapeutic.

How bold is blood oxygenation level-dependent (BOLD) magnetic resonance imaging of the kidney? Opportunities, challenges and future directions.

Renal tissue hypoperfusion and hypoxia are key elements in the pathophysiology of acute kidney injury and its progression to chronic kidney disease. Yet, in vivo assessment of renal haemodynamics and tissue oxygenation remains a challenge. Many of the established approaches are invasive, hence not applicable in humans. Blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) offers an alternative. BOLD-MRI is non-invasive and indicative of renal tissue oxygenation. Nonetheless, recent (pre-) clinical studies revived the question as to how bold renal BOLD-MRI really is. This review aimed to deliver some answers. It is designed to inspire the renal physiology, nephrology and imaging communities to foster explorations into the assessment of renal oxygenation and haemodynamics by exploiting the powers of MRI. For this purpose, the specifics of renal oxygenation and perfusion are outlined. The fundamentals of BOLD-MRI are summarized. The link between tissue oxygenation and the oxygenation-sensitive MR biomarker T2∗ is outlined. The merits and limitations of renal BOLD-MRI in animal and human studies are surveyed together with their clinical implications. Explorations into detailing the relation between renal T2∗ and renal tissue partial pressure of oxygen (pO2 ) are discussed with a focus on factors confounding the T2∗ vs. tissue pO2 relation. Multi-modality in vivo approaches suitable for detailing the role of the confounding factors that govern T2∗ are considered. A schematic approach describing the link between renal perfusion, oxygenation, tissue compartments and renal T2∗ is proposed. Future directions of MRI assessment of renal oxygenation and perfusion are explored.

Early effects of an x-ray contrast medium on renal T(2) */T(2) MRI as compared to short-term hyperoxia, hypoxia and aortic occlusion in rats.

AIM: X-ray contrast media (CM) can cause acute kidney injury (AKI). Medullary hypoxia is pivotal in CM-induced AKI, as indicated by invasively and pin-point measured tissue oxygenation. MRI provides spatially resolved blood oxygenation level-dependent data using T2 * and T2 mapping. We studied CM effects on renal T2 */T2 and benchmarked them against short periods of hyperoxia, hypoxia and aortic occlusion (AO). METHODS: Rats were equipped with carotid artery catheters (tip towards aorta) and supra-renal aortic occluders. T2 */T2 mapping was performed using a 9.4-T animal scanner. CM (1.5 mL iodixanol) was injected into the thoracic aorta with the animal in the scanner followed by 2 h of T2 */T2 mapping. For T2 */T2 assessment, regions of interest in the cortex (C), outer medulla (OM), inner medulla (IM) and papilla (P) were determined according to morphological features. RESULTS: Hyperoxia increased T2 * in C (by 17%) and all medullary layers (25-35%). Hypoxia decreased T2 * in C (40%) and all medullary layers (55-60%). AO decreased T2 * in C (18%) and all medullary layers (30-40%). Upon injection of CM, T2 * increased transiently, then decreased, reaching values 10-20% below baseline in C and OM and 30-40% below baseline in IM and P. CONCLUSION: T2 * mapping corroborates data previously obtained with invasive methods and demonstrates that CM injection affects renal medullary oxygenation. CM-induced T2 * decrease in OM was small vs. hypoxia and aortic occlusion. T2 * decrease obtained for hypoxia was more pronounced than for AO. This indicates that T2 * may not accurately reflect blood oxygenation under certain conditions.

Linking non-invasive parametric MRI with invasive physiological measurements (MR-PHYSIOL): towards a hybrid and integrated approach for investigation of acute kidney injury in rats.

Acute kidney injury of various origins shares a common link in the pathophysiological chain of events: imbalance between renal medullary oxygen delivery and oxygen demand. For in vivo assessment of kidney haemodynamics and oxygenation in animals, quantitative but invasive physiological methods are established. A very limited number of studies attempted to link these invasive methods with parametric Magnetic Resonance Imaging (MRI) of the kidney. Moreover, the validity of parametric MRI (pMRI) as a surrogate marker for renal tissue perfusion and renal oxygenation has not been systematically examined yet. For this reason, we set out to combine invasive techniques and non-invasive MRI in an integrated hybrid setup (MR-PHYSIOL) with the ultimate goal to calibrate, monitor and interpret parametric MR and physiological parameters by means of standardized interventions. Here we present a first report on the current status of this multi-modality approach. For this purpose, we first highlight key characteristics of renal perfusion and oxygenation. Second, concepts for in vivo characterization of renal perfusion and oxygenation are surveyed together with the capabilities of MRI for probing blood oxygenation-dependent tissue stages. Practical concerns evoked by the use of strong magnetic fields in MRI and interferences between MRI and invasive physiological probes are discussed. Technical solutions that balance the needs of in vivo physiological measurements together with the constraints dictated by small bore MR scanners are presented. An early implementation of the integrated MR-PHYSIOL approach is demonstrated including brief interventions of hypoxia and hyperoxia.

Sinonasal persistence of Pseudomonas aeruginosa after lung transplantation.

UNLABELLED: We report on two CF patients who received double lung transplantation (LTX) due to Pseudomonas aeruginosa related pulmonary destruction. Prior to LTX we detected P. aeruginosa in nasal lavages (NL) and sputum cultures from both patients. Donor lungs of patient 1 became colonized within four weeks with P. aeruginosa identical in genotype with isolates from his pre-transplant sputum cultures and pre- and post-transplant NL. In contrast, patient 2 remained P. aeruginosa free in lower airway samples (bronchial lavage/sputum) for now up to 30 months, despite persistent detection of P. aeruginosa that was identical in genotype with pre-transplant NL and sputum isolates in NL and even in throat swabs. For prevention of pulmonary re-colonization patient 2 has continuously inhaled Colomycin 1 MIU once daily during the preceding more than 36 months with the novel Pari Sinus™ nebulizer, which in scintigraphic studies was shown to deliver vibrating aerosols into paranasal sinuses, additional to bronchial antibiotic inhalation. DISCUSSION: Pulmonary colonization of transplanted donor lungs with identical clones previously colonizing the explanted lungs has been described previously and the upper airways were postulated as reservoir for descending colonization. However, this remained speculative, as upper airway sampling which does not belong to current standards, was not performed in these studies. Our report demonstrates persistence of identical P. aeruginosa genotypes in CF upper airways prior to and after LTX underlining risks of descending colonization of transplanted lungs with P. aeruginosa, which increases risks of graft dysfunction. Therefore, we recommend regular assessment of sinonasal colonization prior to and after LTX. Sinonasal inhalation with antimicrobials should be investigated in prospective trials.

A Novel Homozygous WDR72 Mutation in Two Siblings with Amelogenesis Imperfecta and Mild Short Stature.

Amelogenesis imperfecta (AI) is a clinically and genetically heterogeneous group of inherited defects of enamel formation. In isolated AI (no additional segregating features), mutations in at least 7 genes are known so far, causing dominant, recessive or X-linked AI and allowing the identification of the molecular etiology in 40-50% of affected families. We report on 2 siblings (an 11-year-old female and a 7-year-old male) born to consanguineous Turkish parents, with AI and mild, proportionate short stature. Both parents have normal teeth, but mother, maternal grandmother and great-grandfather are/were also of short stature. A spine X-ray performed in the girl excluded brachyolmia. Affymetrix GenomeWide SNP6.0 Array analysis identified no pathogenic copy number changes, but showed sharing of large homozygous regions, including chromosome band 15q21.3 containing the WDR72 gene. WDR72 sequence analysis in both siblings revealed homozygosity for a novel stop mutation in exon 10 (c.997A>T, p.Lys333X) explaining the AI phenotype. Mutations in WDR72 are a very rare cause of autosomal-recessive hypomaturation type of isolated AI. The mutation described in our patients specifies the diagnosis AI IIA3 and represents only the sixth WDR72 mutation reported so far. The WDR72 protein is critical for dental enamel formation, but its exact function is still unknown.

DNA methylation studies on imprinted loci in a male monozygotic twin pair discordant for Beckwith-Wiedemann syndrome.

Beckwith­Wiedemann syndrome (BWS) is one of the most prevalent congenital disorders predominantly caused by epigenetic alterations. Here we present an extensive case study of a monozygotic monochorionic male twin pair discordant for BWS. Our analysis allows to correlate BWS symptoms, like a protruding tongue, indented ears and transient neonatal hypoglycaemia, to an abnormal methylation at the KvDMR1. DNAs extracted from peripheral blood, skin fibroblasts, saliva and buccal swab of both twins, their sister and parents were analysed at 11 differentially methylated regions (DMRs) including all four relevant DMRs of the BWS region. The KvDMR1 was exclusively found to be hypomethylated in all cell types of the affected BWS twin, while the unaffected twin and the relatives showed normal methylation in fibroblasts, buccal swab and saliva DNA. Interestingly, the twins share a common blood-specific hypomethylation phenotype most probably caused by a feto-fetal transfusion between both twins. Because microsatellite analysis furthermore revealed a normal biparental karyotype for chromosome 11, our results point to an exclusive correlation of the observed BWS symptoms to locally restricted epimutations at the KvDMR1 of the maternal chromosome.

mRNA expression and protein distribution of fibronectin splice variants and high-molecular weight tenascin-C in different phases of human fracture healing.

Fracture healing is a reparative physiological process, which proceeds in stages, each characterized by the predominant tissue in the fracture gap. The tissue matrix is continuously reorganized by cell migration, proliferation, and differentiation. Adhesive proteins such as fibronectin and tenascin transmit information between matrix and cells. As a result of alternative splicing of pre-RNA, EDA + fibronectin, EDB + fibronectin, and high-molecular weight (hm) tenascin-C are generated. By definition, EDB + fibronectin is an oncofetal protein because it is extremely rare in normal adult tissue and plasma, whereas it is expressed in fetal and tumor tissues and during wound healing. In this study, we for the first time describe EDA + fibronectin, EDB + fibronectin, and hm tenascin-C expression in human fracture gap tissue during various stages of differentiation. We demonstrate mRNA expression of all three splice variants in the initial fibrin matrix with upregulation in the enchondral ossification/osteoid and woven bone stages. Of all variants, EDA + fibronectin mRNA has the highest concentration in all stages. For the analysis, we used LightCycler-based relative mRNA quantification and immunohistochemistry. Our data demonstrate that EDA + fibronectin and hm tenascin-C show a diffuse distribution pattern in fracture gap connective tissue, while EDB + fibronectin is focally concentrated in osteoblastic cells at the margins of woven bone. EDA + fibronectin and hm tenascin represent markers for active granulation processes, whereas EDB + fibronectin is specific for cells forming the enchondral and osteoid matrix. The possibility of stimulating fracture healing by EDB + fibronectin-cytokine complexes should be tested in further investigations.

[Sonographic diagnosis of caudal regression syndrome]. / Sonografische Diagnose eines kaudalen Regressionssyndroms.

Caudal regression sequence (CRS) is a rare developmental defect of the lower spinal segments and the neural tube. Motor and sensory neurological deficits of the lower extremities as well as a reduced control of bowel and bladder functions are the main symptoms. Etiology and pathogenesis are widely unknown. This article discusses a newborn male with postnatal anomalies of the lower extremities. Sonographically, the spinal cord ended in the lumbar region. NMR confirmed the suspected sonographic finding of CRS. Sonographic examination of the abdominal vessel system depicted a common origin and junction of the hepatic artery, splenic artery and superior mesenteric artery from one common truncus. This points to a possible relict of a persisting vitelline artery. As previously described in sirenomelia, the findings in the present case indicate a possible vascular etiology of CRS.

[Changes in shape and size of the foot during pregnancy]. / Form- und Grössenveränderungen des Fusses während der Schwangerschaft.

Many women report an increase in foot size during their pregnancy. Our objective was to verify this anecdotal evidence. In an initial survey of 21 mothers in 2 Münster nursery schools we found a tendency towards an increase in foot size during pregnancy. We therefore developed a measuring system to measure changes in foot length, width, height and volume. A total of 40 women recruited from the antenatal clinic of the University Hospital of Münster and a participating practice were seen three times during their pregnancy. The results were analysed using the Wilcoxon test. We found a statistically significant increase in foot length, width and volume, whereas foot height decreased slightly. This difference was, however, not significant. Especially in diabetic women with polyneuropathy it is important to pay attention to shoe size to prevent pressure sores.

Caudal regression sequence: vascular origin?

Caudal regression sequence (CRS) is a rare congenital defect of the lower spinal segments and the neural tube. Motor symptoms as well as neurological deficits and loss of bladder and bowel function are usually present. CRS is also associated with anomalies in other systems such as the gastrointestinal and genitourinary tract. Etiology and pathogenesis are poorly understood.A newborn presented with anomalies of the spinal column (lumbosacral) with absence/hypoplasia of the 12th thoracic and first lumbar vertebral anomaly body. Bladder and bowel initially were functional. MR-angiography exhibited an anomaly of the unpaired vessels originating from the aorta, a likely relict of a persisting vitelline artery. These findings indicate a potential vascular genesis of CRS, much as in sirenomelia.

Prospective surveillance of nosocomial infections in a Swiss NICU: low risk of pneumonia on nasal continuous positive airway pressure?

BACKGROUND: This study assessed the rate of invasive nosocomial infections in very low birth weight (VLBW) 1,500 g, who had received a central venous or umbilical catheter, or assisted ventilation. Nosocomial infections (sepsis, pneumonia, necrotizing enterocolitis [NEC]) were defined according to Centers for Disease Control (CDC) recommendations with slight modifications and their rates measured longitudinally. RESULTS: Among VLBW neonates, 16 nosocomial infections for an overall infection rate of 6 per 1,000 patient days were found. Infants with infection were of lower birth weight, a greater proportion was male, received lipid infusions, and on average had a higher severity of illness (CRIB) score. Interestingly, the ventilator-associated pneumonia (VAP) rate (12.5/1,000 ventilator days) seemed significantly higher than the pneumonia rate during nasal continuous positive airway pressure (NCPAP) treatment (1.8/1,000 NCPAP days; p = 0.04). The sepsis rate associated with peripheral catheters almost equaled the central line-associated rate, although numbers for both device-related infections were small. CONCLUSION: Further studies are needed to confirm the observation that the NCPAP-associated pneumonia rate might be lower than the VAP rate in VLBW infants, as well as to confirm the second observation that the sepsis rates on peripheral catheters compared to central venous catheters might be almost equal in VLBW infants. Reducing the exposure to ventilation via endotracheal tube, but not using peripheral as opposed to central catheters, might reduce the incidence of device-associated infection in this patient population.

Refilling of cortical calcium stores in Paramecium cells: in situ analysis in correlation with store-operated calcium influx.

This is the first thorough study of refilling of a cortical calcium store in a secretory cell after stimulation in which we combined widely different methodologies. Stimulation of dense-core vesicle ("trichocysts") exocytosis in Paramecium involves a Ca(2+) -influx" superimposed to Ca(2+) -release from cortical stores ("alveolar sacs" (ASs)). In quenched-flow experiments, membrane fusion frequency rose with increasing [Ca(2+)](o) in the medium, from approximately 20-25% at [Ca(2+)](o) < or = 0.25 microM to 100% at [Ca(2+)](o) between 2 and 10 microM, i.e. close to the range of estimated local intracellular [Ca(2+)] during membrane fusion. Next, we analyzed Ca(2+)-specific fluorochrome signals during stimulation under different conditions. Treatment with actin-reactive drugs had no effect on Ca(2+) -signaling. In double trigger experiments, with BAPTA in the second secretagogue application (BAPTA only for stimulation and analysis), the cortical Ca(2+) -signal (due solely to Ca(2+) released from cortical stores) recovered with t(1/2) approximately 65 min. When ASs were analyzed in situ by X-ray microanalysis after different trigger times (+Ca(2+)(o)), t(1/2) for store refilling was similar, approximately 60 min. These values are similar to previously measured 45Ca(2+) -uptake by isolated ASs. In sum we find, (i) exogenous Ca(2+) increases exocytosis/membrane fusion performance with EC(50)=0.7 microM, (ii) Ca(2+) -signaling in this system is not sensitive to actin-reactive drugs, and (iii) refilling of these cortical calcium stores goes on over hours and thus is much slower than expected.

Functional and fluorochrome analysis of an exocytotic mutant yields evidence of store-operated Ca2+ influx in Paramecium.

A non-discharge mutant of Paramecium tetraurelia (nd12-35 degrees C, lacking exocytotic response upon stimulation with the nonpermeable polycationic secretagogue aminoethyldextran, AED), in the pawnA genetic context (d4-500r, lacking ciliary voltage-dependent Ca2+ influx), was shown to lack (45)Ca2+ entry from outside upon AED stimulation. In contrast, cells grown at 25 degrees C behave like the wildtype. To check the functional properties in more detail, fluorochrome-loaded 35 degrees C cells were stimulated, not only with AED (EC(100) = 10(-6) M in wildtype cells), but also with 4-chloro-meta-cresol, (4CmC, 0.5 mM), a permeable activator of ryanodine receptor-type Ca2+ release channels, usually at extracellular [Ca2+] of 50 microM, and eventually with a Ca2+ chelator added. We confirm that pwA-nd12(35 degrees C) cells lack any Ca2+ influx and any exocytosis of trichocysts in response to any stimulus. As we determined by x-ray microanalysis, total calcium content in alveolar sacs (subplasmalemmal stores) known to be mobilized upon exocytosis stimulation in wild-type cells, contain about the same total calcium in 35 degrees C as in 25 degrees C cells, and Ca2+ mobilization from alveoli by AED or 4CmC is also nearly the same. Due to the absence of any AED-induced Ca2+ influx in 35 degrees C cells and normal Ca2+ release from stores found by x-ray microanalysis one can exclude a "CICR"-type mechanism (Ca2+-induced Ca2+ release) and imply that normally a store-operated Ca2+ ("SOC") influx would occur (as in 25 degrees C cells). Furthermore, 35 degrees C cells display a significantly lower basal intracellular [Ca2+], so that any increase upon stimulation may be less expressed or even remain undetected. Under these conditions, any mobilization of Ca2+ from stores cannot compensate for the lack of Ca2+ influx, particularly since normally both components have to cooperate to achieve full exocytotic response. Also striking is our finding that 35 degrees C cells are unable to perform membrane fusion, as analyzed with the Ca2+ ionophore, A23187. These findings were corroborated by cryofixation and freeze-fracture analysis of trichocyst docking sites after AED or 4CmC stimulation, which also revealed no membrane fusion. In sum, in nd12 cells increased culture temperature entails multiple defects, notably insensitivity to any Ca2+ signal, which, moreover, cannot develop properly due to a lower basal [Ca2+] level and the lack of Ca2+ influx, despite normal store activation.

Role of erythromycin for treatment of incipient chronic lung disease in preterm infants colonised with Ureaplasma urealyticum.

Ureaplasma urealyticum is frequently isolated from tracheal aspirates of very low birthweight infants who go on to develop chronic lung disease. The use of erythromycin has been advocated in ventilated very low birthweight infants who are colonised with U. urealyticum, although the association between U. urealyticum and chronic lung disease remains controversial. There are only two randomised, controlled trials involving a total of 37 U. urealyticum-positive very low birthweight infants. Both trials failed to demonstrate a reduction in the incidence of chronic lung disease after 7 or 10 days of erythromycin. On the other hand, there are reports of rare but serious adverse effects of erythromycin in newborn infants including sudden cardiovascular compromise and hypertrophic pyloric stenosis. We conclude that, at present, there is insufficient evidence to support the use of erythromycin for the treatment of incipient chronic lung disease in very low birthweight infants colonised with U. urealyticum.

Liver support by extracorporeal blood purification: a clinical observation.

Liver failure associated with excretory insufficiency and jaundice results in an endogenous accumulation of toxins involved in the impairment of cardiovascular, kidney, and cerebral function. Moreover, these toxins have been shown to damage the liver itself by inducing hepatocellular apoptosis and necrosis, thus creating a vicious cycle of the disease. We report a retrospective cohort study of 26 patients with acute or chronic liver failure with intrahepatic cholestasis (bilirubin level > 20 mg/dL) who underwent a new extracorporeal blood purification treatment. A synthetic hydrophilic/hydrophobic domain-presenting semipermeable membrane (pore size < albumin size, 100-nm thick) was used for extracorporeal blood detoxification using dialysis equipment. The opposite side was rinsed with ligandin-like proteins as molecular adsorbents that were regenerated online using a chromatography-like recycling system (molecular adsorbent recirculating system [MARS]). Bile acid and bilirubin levels, representing the previously described toxins, were reduced by 16% to 53% and 10% to 90% of the initial concentration by a single treatment of 6 to 8 hours, respectively. Toxicity testing of patient plasma onto primary rat hepatocytes by live/dead fluorescence microscopy showed cell-damaging effects of jaundiced plasma that were not observed after treatment. Patients with a worsening of Child-Turcotte-Pugh (CTP) index before the treatments showed a significant improvement of this index during a period of 2 to 14 single treatments with an average of 14 days. After withdrawal of MARS treatment, this improvement was sustained in all long-term survivors. Ten patients represented a clinical status equivalent to the United Network for Organ Sharing (UNOS) status 2b (group A1), and all survived. Sixteen patients represented a clinical status equivalent to UNOS status 2a, and 7 of these patients survived (group A2), whereas 9 patients (group B) died. We conclude that in acute excretory failure caused by a chronic liver disease, this treatment provides a therapy option to remove toxins involved in multiorgan dysfunction secondary to liver failure.

[1H-MR spectroscopy in anorexia nervosa: the characteristic differences between patients and healthy subjects]. / 1H-MR-Spektroskopie bei Anorexia nervosa: charakteristische Unterschiede zwischen Patienten und gesunden Probanden.

PURPOSE: The neurophysiological and neuromorphological changes in patients with anorexia nervosa (AN) are well-known but the reason of both is still unknown. We have evaluated the usefulness of hydrogen (H1) magnetic resonance spectroscopy in anorexia nervosa. METHOD: We investigated 15 patients with clinically diagnosed AN (ICD F50.0) and 17 controls without eating disorders. The body mass index (BMI) was 15.8 and 21, respectively. The spectroscopy was recorded on two voxels in the parieto-occipital white matter or in the thalamus with a water-suppressed STEAM-sequence. The metabolites were recorded with respect to phosphocreatine (PCr). RESULTS: The ratio of NAA/PCr in both voxels were not significantly different when comparing patients vs. controls. Patients showed significantly higher ratios of choline-containing components (Cho) or, respectively Cho/PCr and NAA/PCr in the white matter. Distinct, but not significant differences were detected both for m-Ino and m-Ino/PCr in the parieto-occipital region and for the Cho- and m-Ino contained ratios in the thalamus. CONCLUSION: AN is not associated with neuronal damage. The ratio of Cho/PCr and NAA/Cho may reflect the disturbance of membrane-turnover. It is possible that the increase of membrane catabolism leads to a hyperosmolar state. The change of m-Ino/PCr ratio may reflect the regulation of osmolarity.

Neonatal nosocomial infection surveillance: incidences by site and a cluster of necrotizing enterocolitis.

Nosocomial infection (NI) was prospectively studied in hospitalized neonates during a 10-month period. The Centers for Disease Control (CDC) criteria (some specified for neonates) were used for surveillance. Forty-nine of 677 infants experienced 73 episodes of NI. The overall incidence was 10.8 NI/100 patients and 6.5 NI/1,000 patient days. The average monthly NI number did not correlate with patient load. Very low birth weight (VLBW) infants showed a higher NI incidence (81.8 NI/100 patients and 11.1 NI/1,000 patient days), also elevated if adjusted for their inherently longer neonatal intensive care unit (NICU) stay. The most common NI sites in the VLBW stratum were sepsis and necrotizing enterocolitis (NEC), the latter occurring in a seasonal cluster. It can be concluded that surveillance for NIs should focus on VLBW infants and include the evaluation of NEC, as it behaves like a nosocomial disease.