The Presence of Portal Vein Thrombosis Alters the Classic Enhancement Associated with Diagnosis of Hepatocellular Carcinoma

Digestive Diseases and Sciences - To determine whether the presence of portal vein thrombosis (PVT) where venous flow within the liver may be altered may delay the diagnosis of HCC and be...     

Rapid Progression of Native Renal Artery Fibromuscular Dysplasia Following Kidney Donation

Fibromuscular dysplasia is the second commonest anatomical abnormality apart from multiple renal arteries in the potential live donors. Pretransplant evaluation of the donors may include an angiography to evaluate the renal arteries, and failure to recognize renal arterial stenosis, particularly fibromuscular dysplasia, by noninvasive methods may eventually lead to hypertension and ischemic renal failure. We report a case of fibromuscular dysplasia that was undetected by computed tomographic angiography prior to donation. One year after kidney donation, it rapidly progressed to severe symptomatic stenosis with hypertension and acute renal failure. Following renal artery angioplasty, her blood pressure normalized over a period of 2 weeks without any need for antihypertensive medications and the serum creatinine returned to her baseline. The acceptability of renal donors with fibromuscular dysplasia depends on the age, race and the availability of the other suitable donors. Mild fibromuscular dysplasia in a normotensive potential renal donor cannot be considered a benign condition. Such donors need regular follow-up postdonation for timely detection and treatment.     

Leakage associated with intermediate restorative material and glass-ionomer cement retrograde fillings: a human and sheep teeth comparison with 2 different aging procedures.

OBJECTIVES: Leakage around retrograde fillings is an important cause of endodontic surgery. This in vitro study sought to compare the following: (1) methylene blue dye leakage linked to retrofillings in human and sheep teeth with the degree of dye penetration when intermediate restorative materials and Chemfil were used as retrofillings, (2) the apical microleakage in filled with that in unfilled root canals, and (3) 2 storage techniques, incubator-based and subcutaneous implantation in rats. STUDY DESIGN: Tested were 198 human and 196 sheep teeth that were retrofilled with intermediate restorative material or Chemfil, then stored in an incubator or subcutaneously in rats for 10, 20, and 30 days before immersion in methylene blue dye for 24 hours. Linear dye penetration was evaluated, and the results were statistically analyzed by means of analysis of variance. RESULTS: Leakage between sheep and human teeth was significantly different (P <.05). Chemfil had significantly less leakage than intermediate restorative material after storage in rat (P <.05) for up to 20 days, but not after 30 days. No differences were found between leakage of unfilled and filled human root canal teeth. CONCLUSIONS: The sheep incisor is a poor experimental model of the human tooth, and both aging procedures demonstrate extensive leakage of retrofilling materials after long-term storage.     

Neural network models for the gaze shift system in the superior colliculus and cerebellum.

We investigate the role that the superior colliculus (SC) and the cerebellum might play in generating gaze shifts. The discharge of cells in the intermediate layers of the SC is tightly linked to the occurrence of saccades. Many studies have demonstrated that the cerebellum is involved in both eye and head movements. When the head is unrestrained, large amplitude gaze shifts are composed of coordinated eye and head movements. In this study, we propose that the gaze saccades system is controlled by a feedback loop between the SC and the cerebellum. The SC only encodes retinal coordinates and controls the eye displacement (to move the fovea to the target), while the cerebellum deals with the gaze programming and controls the head displacement. When a target appears in space, the buildup cells within the SC decode the target signal in the retina before the saccade onset, and input the signal of the gaze displacement to the cerebellum. The cells in the cerebellum vermis encode the initial position of the eye in the orbit. The gaze displacement is decomposed into the head amplitude and the eye amplitude within the cerebellum. There are two output signals from the cerebellum. One signal controls the head movement. The other is projected back to the SC, and forms a component of the saccade vector to control the eye movement. The sum of the vectors provided by the cerebellum and the vector provided by the burst cells in the SC indicates the direction and the amplitude of the desired movement of the eye during the saccade. We propose a cerebellum model to predict the displacements of the eye and head under the condition that the position of the target signal in the retina and the initial position of the eye in the orbit are known. The results from the model are close to that observed physiologically. We conclude that before gaze shift onset, the cerebellum may play an important role in decomposing the gaze displacement into an eye amplitude and head amplitude signal.     

Percutaneous transluminal angioplasty of tibial arteries for limb salvage

Percutaneous transluminal balloon angioplasty (PTA) was performed in 17 tibial arteries with an average cross-sectional area stenosis of 92% (range 75–99%) in 13 patients (14 limbs) for limb salvage. In 4 of 14 lower extremities, PTA of femoropopliteal arteries was also performed. Technical success with 50% or less residual stenosis was achieved in all 17 tibial vessels. At approximately 2 months after PTA, clinical improvement had occurred in 10 of 14 limbs; no patient was made worse. Most recent follow-up (mean 19 months, range 8–34 months) revealed continued satisfactory clinical success with no further vascular intervention in 9 of these 10 limbs (one patient died). Short segmental stenoses, residual stenoses less than 40% following PTA, and absence of diabetes or gangrene appear to be predictors of favorable clinical outcomes. Our results suggest that PTA of focal tibial stenosis is an effective and safe treatment modality in properly selected patients and that wider use of PTA may be justified.     

Wilms tumor in patients with osteopathia striata with cranial sclerosis

Germline pathogenic variants in AMER1 cause osteopathia striata with cranial sclerosis (OSCS: OMIM 300373), an X-linked sclerosing bone disorder. Female heterozygotes exhibit metaphyseal striations in long bones, macrocephaly, cleft palate, and, occasionally, learning disability. Male hemizygotes typically manifest the condition as fetal or neonatal death. Somatically acquired variants in AMER1 are found in neoplastic tissue in 15–30% of patients with Wilms tumor; however, to date, only one individual with OSCS has been reported with a Wilms tumor. Here we present four cases of Wilms tumor in unrelated individuals with OSCS, including the single previously published case. We also report the first case of bilateral Wilms tumor in a patient with OSCS. Tumor tissue analysis showed no clear pattern of histological subtypes. In Beckwith–Wiedemann syndrome, which has a known predisposition to Wilms tumor development, clinical protocols have been developed for tumor surveillance. In the absence of further evidence, we propose a similar protocol for patients with OSCS to be instituted as an initial precautionary approach to tumor surveillance. Further evidence is needed to refine this protocol and to evaluate the possibility of development of other neoplasms later in life, in patients with OSCS.Subject terms: Genetics, Clinical genetics, Disease genetics     

Organ-preference of metastasis

Summary The initial, site-specific colonization of secondary organs by blood-borne cancer cells appears to be mediated by endothelial cell adhesion molecules. These molecules are part of the organ-specific microvascular phenotype and are regulated through complex interactions of the endothelium with the extracellular matrix (e.g., distinct matrix macromolecules and growth factors). They are inducedin vitro by growing unspecific (large vessel) endothelial cells on extracts of organ-specific biomatrices. In many respects, these molecules are similar to the various classes of chemically different adhesion molecules that regulate lymphocyte traffic, but are believed to be distinct from the inducible adhesion molecules that govern leukocyte adhesion during acute episodes of inflammation. Biochemical and biophysical data indicate that preference of tumor cell adhesion to organ-specific microvascular endothelium may not require qualitative differences of such homing receptors between endothelia, but may be explained on the basis of quantitative receptor differences as well as differences of receptor avidity. Following adhesion, the metastatic cascade proceeds by the establishment of metabolic conduits between the endothelium and adherent tumor cells. This heterotypic coupling represents an early step in the extravasation of cancer cells from the microvasculature, initiating endothelial cell retraction from its basement membrane and recanalization around the arrested tumor cell. These events, together with local growth promoting effects exerted by the metastasized organ, are believed to provide the basis for Paget's seed and soil hypothesis of metastasis.     

Expanding allelic and phenotypic spectrum of ZC4H2-related disorder: A novel hypomorphic variant and high prevalence of tethered cord

ZC4H2 (MIM# 300897) is a nuclear factor involved in various cellular processes including proliferation and differentiation of neural stem cells, ventral spinal patterning and osteogenic and myogenic processes. Pathogenic variants in ZC4H2 have been associated with Wieacker-Wolff syndrome (MIM# 314580), an X-linked neurodevelopmental disorder characterized by arthrogryposis, development delay, hypotonia, feeding difficulties, poor growth, skeletal abnormalities, and dysmorphic features. Zebrafish zc4h2 null mutants recapitulated the human phenotype, showed complete loss of vsx2 expression in brain, and exhibited abnormal swimming and balance problems. Here we report 7 new patients (four males and three females) with ZC4H2-related disorder from six unrelated families. Four of the 6 ZC4H2 variants are novel: three missense variants, designated as c.142T>A (p.Tyr48Asn), c.558G>A (p.Met186Ile) and c.602C>T (p.Pro201Leu), and a nonsense variant, c.618C>A (p.Cys206*). Two variants were previously reported : a nonsense variant c.199C>T (p.Arg67*) and a splice site variant (c.225+5G>A). Five patients were on the severe spectrum of clinical findings, two of whom had early death. The male patient harboring the p.Met186Ile variant and the female patient that carries the p.Pro201Leu variant have a relatively mild phenotype. Of note, 4/7 patients had a tethered cord that required a surgical repair. We also demonstrate and discuss previously under-recognized phenotypic features including sleep apnea, arrhythmia, hypoglycemia, and unexpected early death. To study the effect of the missense variants, we performed microinjection of human ZC4H2 wild-type or variant mRNAs into zc4h2 null mutant zebrafish embryos. The p.Met186Ile mRNA variant was able to partially rescue vsx2 expression while p.Tyr48Asn and p.Pro201Leu mRNA variants were not. However, swimming and balance problems could not be rescued by any of these variants. These results suggest that the p.Met186Ile is a hypomorphic allele. Our work expands the genotypes and phenotypes associated with ZC4H2-related disorder and demonstrates that the zebrafish system is a reliable method to determine the pathogenicity of ZC4H2 variants.     

Cybersecurity for Cardiac Implantable Electronic Devices: What Should You Know?

Medical devices have been targets of hacking for over a decade, and this cybersecurity issue has affected many types of medical devices. Lately, the potential for hacking of cardiac devices (pacemakers and defibrillators) claimed the attention of the media, patients, and health care providers. This is a burgeoning problem that our newly electronically connected world faces. In this paper from the Electrophysiology Section Council, we briefly discuss various aspects of this relatively new threat in light of recent incidents involving the potential for hacking of cardiac devices. We explore the possible risks for the patients and the effect of device reconfiguration in an attempt to thwart cybersecurity threats. We provide an outline of what can be done to improve cybersecurity from the standpoint of the manufacturer, government, professional societies, physician, and patient.